Biochmical et Biophysica Acta - General Subjects

Syndicate content ScienceDirect Publication: Biochimica et Biophysica Acta (BBA) - General Subjects
ScienceDirect RSS
Updated: 1 year 50 weeks ago

Iron-associated biology of Trypanosoma brucei

Mon, 11/30/2015 - 08:11
Publication date: February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 2

Author(s): Somsuvro Basu, Eva Horáková, Julius Lukeš

Background Every eukaryote requires iron, which is also true for the parasitic protist Trypanosoma brucei, the causative agent of sleeping sickness in humans and nagana in cattle. T. brucei undergoes a complex life cycle during which its single mitochondrion is subject to major metabolic and morphological changes. Scope of review This review covers what is known about processes associated with iron–sulfur clusters and heme metabolism in T. brucei. We discuss strategies by which iron and heme are acquired and utilized by this model parasite, emphasizing the differences between its two life cycle stages residing in the bloodstream of the mammalian host and gut of the insect vector. Finally, the role of iron in the host–parasite interactions is discussed along with their possible exploitation in fighting these deadly parasites. Major conclusions The processes associated with acquisition and utilization of iron, distinct in the two life stages of T. brucei, are fine tuned for the dramatically different host environment occupied by them. Although the composition and compartmentalization of the iron–sulfur cluster assembly seem to be conserved, some unique features of the iron acquisition strategies may be exploited for medical interventions against these parasites. General significance As early-branching protists, trypanosomes and related flagellates are known to harbor an array of unique features, with the acquisition of iron being another peculiarity. Thanks to intense research within the last decade, understanding of iron–sulfur cluster assembly and iron metabolism in T. brucei is among the most advanced of all eukaryotes.





Preferential nitrite inhibition of the mitochondrial F1FO-ATPase activities when activated by Ca2+ in replacement of the natural cofactor Mg2+

Mon, 11/30/2015 - 08:11
Publication date: February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 2

Author(s): Salvatore Nesci, Vittoria Ventrella, Fabiana Trombetti, Maurizio Pirini, Alessandra Pagliarani


Graphical abstract




Influence of a family 29 carbohydrate binding module on the activity of galactose oxidase from Fusarium graminearum

Mon, 11/30/2015 - 08:11
Publication date: February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 2

Author(s): Filip Mollerup, Kirsti Parikka, Thu V. Vuong, Maija Tenkanen, Emma Master

Background Galactose oxidase (GaO) selectively oxidizes the primary hydroxyl of galactose to a carbonyl, facilitating targeted chemical derivatization of galactose-containing polysaccharides, leading to renewable polymers with tailored physical and chemical properties. Here we investigate the impact of a family 29 glucomannan binding module on the activity and binding of GaO towards various polysaccharides. Specifically, CBM29-1-2 from Piromyces equi was separately linked to the N- and C-termini of GaO. Results Both GaO–CBM29 and CBM29–GaO were successfully expressed in Pichia pastoris, and demonstrated enhanced binding to galactomannan, galactoglucomannan and galactoxyloglucan. The position of the CBM29 fusion affected the enzyme function. Particularly, C-terminal fusion led to greatest increases in galactomannan binding and catalytic efficiency, where relative to wild-type GaO, k cat /K m values increased by 7.5 and 19.8 times on guar galactomannan and locust bean galactomannan, respectively. The fusion of CBM29 also induced oligomerization of GaO–CBM29. Major conclusions Similar to impacts of cellulose-binding modules associated with cellulolytic enzymes, increased substrate binding impeded the action of GaO fusions on more concentrated preparations of galactomannan, galactoglucomannan and galactoxyloglucan; this was especially true for GaO–CBM29. Given the N-terminal positioning of the native galactose-binding CBM32 in GaO, the varying impacts of N-terminal versus C-terminal fusion of CBM29-1-2 may reflect competing action of neighboring CBMs. General significance This study thoroughly examines and discusses the effects of CBM fusion to non-lignocellulytic enzymes on soluble polysaccharides. Herein kinetics of GaO on galactose containing polysaccharides is presented for the first time.





C-termini are essential and distinct for nucleic acid binding of human NABP1 and NABP2

Mon, 11/30/2015 - 08:11
Publication date: February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 2

Author(s): Venkatasubramanian Vidhyasagar, Yujiong He, Manhong Guo, Hao Ding, Tanu Talwar, Vi Nguyen, Jessica Nwosu, George Katselis, Yuliang Wu

Background Human Nucleic Acid Binding Protein 1 and 2 (hNABP1 and 2; also known as hSSB2 and 1, respectively) are two newly identified single-stranded (ss) DNA binding proteins (SSB). Both NABP1 and NABP2 have a conserved oligonucleotide/oligosaccharide-binding (OB)-fold domain and a divergent carboxy-terminal domain, the functional importance of which is unknown. Methods Recombinant hNABP1/2 proteins were purified using affinity and size exclusion chromatography and their identities confirmed by mass spectrometry. Oligomerization state was checked by sucrose gradient centrifugation. Secondary structure was determined by circular dichroism spectroscopy. Nucleic acid binding ability was examined by EMSA and ITC. Results Both hNABP1 and hNABP2 exist as monomers in solution; however, hNABP2 exhibits anomalous behavior. CD spectroscopy revealed that the C-terminus of hNABP2 is highly disordered. Deletion of the C-terminal tail diminishes the DNA binding ability and protein stability of hNABP2. Although both hNABP1 and hNABP2 prefer to bind ssDNA than double-stranded (ds) DNA, hNABP1 has a higher affinity for ssDNA than hNABP2. Unlike hNABP2, hNABP1 protein binds and multimerizes on ssDNA with the C-terminal tail responsible for its multimerization. Both hNABP1 and hNABP2 are able to bind single-stranded RNA, with hNABP2 having a higher affinity than hNABP1. Conclusions Biochemical evidence suggests that the C-terminal region of NABP1 and NABP2 is essential for their functionality and may lead to different roles in DNA and RNA metabolism. General significance This is the first report demonstrating the regulation and functional properties of the C-terminal domain of hNABP1/2, which might be a general characteristic of OB-fold proteins.





Raf kinase inhibitor protein mediated signaling inhibits invasion and metastasis of hepatocellular carcinoma

Mon, 11/30/2015 - 08:11
Publication date: February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 2

Author(s): Xiaohui Wu, Yongjiang Yang, Zhuo Xu, Jiankun Li, Baoming Yang, Ningning Feng, Yueshan Zhang, Shunxiang Wang

Background Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality and poor prognosis. Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways have been implicated in promoting tumor cell proliferation and invasion of HCC cells. Methods As a potential inhibitor of tumor metastasis, the role of Raf kinase inhibitor protein (RKIP) in HCC development and the functional relevance with MAPK and NF-κB signaling pathways were investigated. The levels of RKIP expression were examined in human HCC tissues and correlated with tumor stages and metastatic status. Function of RKIP in cellular proliferation, migration, invasion and apoptosis was investigated in HCC cell lines by either overexpressing or knocking down RKIP expression. Mouse xenograft model was established to assess the effect of RKIP expression on tumor growth. Results Our results demonstrated decreased RKIP expression in HCC tissues and a strong correlation with tumor grade and distant metastasis. Manipulation of RKIP expression in HCCLM3 and HepG2 cells indicated that RKIP functioned to inhibit HCC cell motility and invasiveness, and contributed to tumor growth inhibition in vivo. Mechanistic studies showed that the function of RKIP was mediated through MAPK and NF-κB signaling pathways. However, cell type-dependent RKIP regulation on these two pathways was also suggested, indicating the complex nature of signaling network. Conclusion Our study provides a better understanding on the molecular mechanisms of HCC metastasis and sets the foundation for the development of targeted therapeutics for HCC.





Uptake of Marasmius oreades agglutinin disrupts integrin-dependent cell adhesion

Mon, 11/30/2015 - 08:11
Publication date: February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 2

Author(s): Samuel Juillot, Catherine Cott, Josef Madl, Julie Claudinon, Niels Sebastiaan Johannes van der Velden, Markus Künzler, Roland Thuenauer, Winfried Römer

Background Fruiting body lectins have been proposed to act as effector proteins in the defense of fungi against parasites and predators. The Marasmius oreades agglutinin (MOA) is a lectin from the fairy ring mushroom with specificity for Galα1-3Gal containing carbohydrates. This lectin is composed of an N-terminal carbohydrate-binding domain and a C-terminal dimerization domain. The dimerization domain of MOA shows in addition calcium-dependent cysteine protease activity, similar to the calpain family. Methods Cell detachment assay, cell viability assay, immunofluorescence, live cell imaging and Western blot using MDCKII cell line. Results In this study, we demonstrate in MDCKII cells that after internalization, MOA protease activity induces profound physiological cellular responses, like cytoskeleton rearrangement, cell detachment and cell death. These changes are preceded by a decrease in FAK phosphorylation and an internalization and degradation of β1-integrin, consistent with a disruption of integrin-dependent cell adhesion signaling. Once internalized, MOA accumulates in late endosomal compartments. Conclusion Our results suggest a possible toxic mechanism of MOA, which consists of disturbing the cell adhesion and the cell viability. General significance After being ingested by a predator, MOA might exert a protective role by diminishing host cell integrity.





Editorial Board

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A









Editorial Board

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B









Basic leucine zipper (bZIP) transcription factors involved in abiotic stresses: A molecular model of a wheat bZIP factor and implications of its structure in function

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A

Author(s): Pradeep Sornaraj, Sukanya Luang, Sergiy Lopato, Maria Hrmova

Background Basic leucine zipper (bZIP) genes encode transcription factors (TFs) that control important biochemical and physiological processes in plants and all other eukaryotic organisms. Scope of review Here we present (i) the homo-dimeric structural model of bZIP consisting of basic leucine zipper and DNA binding regions, in complex with the synthetic Abscisic Acid-Responsive Element (ABREsyn); (ii) discuss homo- and hetero-dimerisation patterns of bZIP TFs; (iii) summarise the current progress in understanding the molecular mechanisms of function of bZIP TFs, including features determining the specificity of their binding to DNA cis-elements, and (iv) review information on interaction partners of bZIPs during plant development and stress response, as well as on types and roles of post-translational modifications, and regulatory aspects of protein-degradation mediated turn-over. Finally, we (v) recapitulate on the recent advances regarding functional roles of bZIP factors in major agricultural crops, and discuss the potential significance of bZIP-based genetic engineering in improving crop yield and tolerance to abiotic stresses. Major conclusions An accurate analysis and understanding of roles of plant bZIP TFs in different biological processes requires the knowledge of interacting partners, time and location of expression in plant organs, and the information on mechanisms of homo- and hetero-dimerisation of bZIP TFs. General significance Studies on molecular mechanisms of plant bZIP TFs at the atomic levels will provide novel insights into the regulatory processes during plant development, and responses to abiotic and biotic stresses.





Crystallin biochemistry in health and disease

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B

Author(s): K. Krishna Sharma







CacyBP/SIP — Structure and variety of functions

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A

Author(s): Agnieszka M. Topolska-Woś, Walter J. Chazin, Anna Filipek







Structure and function of α-crystallins: Traversing from in vitro to in vivo

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B

Author(s): Martin Haslbeck, Jirka Peschek, Johannes Buchner, Sevil Weinkauf

Background The two α-crystallins (αA- and αB-crystallin) are major components of our eye lenses. Their key function there is to preserve lens transparency which is a challenging task as the protein turnover in the lens is low necessitating the stability and longevity of the constituent proteins. α-Crystallins are members of the small heat shock protein family. αB-crystallin is also expressed in other cell types. Scope of the review The review summarizes the current concepts on the polydisperse structure of the α-crystallin oligomer and its chaperone function with a focus on the inherent complexity and highlighting gaps between in vitro and in vivo studies. Major conclusions Both α-crystallins protect proteins from irreversible aggregation in a promiscuous manner. In maintaining eye lens transparency, they reduce the formation of light scattering particles and balance the interactions between lens crystallins. Important for these functions is their structural dynamics and heterogeneity as well as the regulation of these processes which we are beginning to understand. However, currently, it still remains elusive to which extent the in vitro observed properties of α-crystallins reflect the highly crowded situation in the lens. General significance Since α-crystallins play an important role in preventing cataract in the eye lens and in the development of diverse diseases, understanding their mechanism and substrate spectra is of importance. To bridge the gap between the concepts established in vitro and the in vivo function of α-crystallins, the joining of forces between different scientific disciplines and the combination of diverse techniques in hybrid approaches are necessary. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.





Effects of cytosine methylation on DNA morphology: An atomic force microscopy study

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A

Author(s): V. Cassina, M. Manghi, D. Salerno, A. Tempestini, V. Iadarola, L. Nardo, S. Brioschi, F. Mantegazza

Methylation is one of the most important epigenetic mechanisms in eukaryotes. As a consequence of cytosine methylation, the binding of proteins that are implicated in transcription to gene promoters is severely hindered, which results in gene regulation and, eventually, gene silencing. To date, the mechanisms by which methylation biases the binding affinities of proteins to DNA are not fully understood; however, it has been proposed that changes in double-strand conformations, such as stretching, bending, and over-twisting, as well as local variations in DNA stiffness/flexibility may play a role. The present work investigates, at the single molecule level, the morphological consequences of DNA methylation in vitro. By tracking the atomic force microscopy images of single DNA molecules, we characterize DNA conformations pertaining to two different degrees of methylation. In particular, we observe that methylation induces no relevant variations in DNA contour lengths, but produces measurable incremental changes in persistence lengths. Furthermore, we observe that for the methylated chains, the statistical distribution of angles along the DNA coordinate length is characterized by a double exponential decay, in agreement with what is predicted for polyelectrolytes. The results reported herein support the claim that the biological consequences of the methylation process, specifically difficulties in protein-DNA binding, are at least partially due to DNA conformation modifications.





Phosphorylation of αB-crystallin: Role in stress, aging and patho-physiological conditions

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B

Author(s): Raman Bakthisaran, Kranthi Kiran Akula, Ramakrishna Tangirala, Ch. Mohan Rao

Background αB-crystallin, once thought to be a lenticular protein, is ubiquitous and has critical roles in several cellular processes that are modulated by phosphorylation. Serine residues 19, 45 and 59 of αB-crystallin undergo phosphorylation. Phosphorylation of S45 is mediated by p44/42 MAP kinase, whereas S59 phosphorylation is mediated by MAPKAP kinase-2. Pathway involved in S19 phosphorylation is not known. Scope of review The review highlights the role of phosphorylation in (i) oligomeric structure, stability and chaperone activity, (ii) cellular processes such as apoptosis, myogenic differentiation, cell cycle regulation and angiogenesis, and (iii) aging, stress, cardiomyopathy-causing αB-crystallin mutants, and in other diseases. Major conclusions Depending on the context and extent of phosphorylation, αB-crystallin seems to confer beneficial or deleterious effects. Phosphorylation alters structure, stability, size distribution and dynamics of the oligomeric assembly, thus modulating chaperone activity and various cellular processes. Phosphorylated αB-crystallin has a tendency to partition to the cytoskeleton and hence to the insoluble fraction. Low levels of phosphorylation appear to be protective, while hyperphosphorylation has negative implications. Mutations in αB-crystallin, such as R120G, Q151X and 464delCT, associated with inherited myofibrillar myopathy lead to hyperphosphorylation and intracellular inclusions. An ongoing study in our laboratory with phosphorylation-mimicking mutants indicates that phosphorylation of R120GαB-crystallin increases its propensity to aggregate. General significance Phosphorylation of αB-crystallin has dual role that manifests either beneficial or deleterious consequences depending on the extent of phosphorylation and interaction with cytoskeleton. Considering that disease-causing mutants of αB-crystallin are hyperphosphorylated, moderation of phosphorylation may be a useful strategy in disease management. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.





Isomerization of aspartyl residues in crystallins and its influence upon cataract

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B

Author(s): Noriko Fujii, Takumi Takata, Norihiko Fujii, Kenzo Aki

Background Age-related cataracts, which probably form due to insolubilization of lens proteins, can lead to loss of vision. Although the exact reason is unknown, lens protein aggregation may be triggered by increases in PTMs such as d-β-, l-β- and d-α-Asp isomers. These isomers have been observed in aged lens; however, there have been few quantitative and site-specific studies owing to the lack of a quick and precise method for distinguishing between d- and l-Asp in a peptide or protein. Scope of review We describe a new method for detecting peptides containing Asp isomers at individual sites in any protein by using an LC–MS/MS system combined with commercial enzymes that specifically react with different isomers. We also summarize current data on the effect of Asp isomerization on lens crystallins. Major conclusions The new technique enabled the analysis of isomers of Asp residues in lens proteins precisely and quickly. An extensive proportion of Asp isomerization was observed at all Asp sites of crystallins in the insoluble fraction of aged lens. In addition, d-amino acid substitutions in crystallin-mimic peptides showed altered structural formation and function. These results indicate that isomerization of Asp residues affects the stability, structure and inter-subunit interaction of lens crystallins, which will induce crystallin aggregation and insolubilization, disrupt the associated functions, and ultimately contribute to the onset of senile cataract formation. General significance The mechanism underlying the onset of age-related diseases may involve isomerization, whereby d-amino acids are incorporated in the l-amino acid world of life. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
Graphical abstract




Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A

Author(s): Laura Pieri, Philippe Chafey, Morgane Le Gall, Guilhem Clary, Ronald Melki, Virginie Redeker


Graphical abstract




The mitochondrial carnitine/acylcarnitine carrier is regulated by hydrogen sulfide via interaction with C136 and C155

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A

Author(s): Nicola Giangregorio, Annamaria Tonazzi, Lara Console, Imma Lorusso, Annalisa De Palma, Cesare Indiveri

Background The carnitine/acylcarnitine carrier (CAC or CACT) mediates transport of acylcarnitines into mitochondria for the β-oxidation. CAC possesses Cys residues which respond to redox changes undergoing to SH/disulfide interconversion. Methods The effect of H2S has been investigated on the [3H]carnitine/carnitine antiport catalyzed by recombinant or native CAC reconstituted in proteoliposomes. Site-directed mutagenesis was employed for identifying Cys reacting with H2S. Results H2S led to transport inhibition, which was dependent on concentration, pH and time of incubation. Best inhibition with IC50 of 0.70μM was observed at physiological pH after 30–60min incubation. At longer times of incubation, inhibition was reversed. After oxidation of the carrier by O2, transport activity was rescued by H2S indicating that the inhibition/activation depends on the initial redox state of the protein. The observed effects were more efficient on the native rat liver transporter than on the recombinant protein. Only the protein containing both C136 and C155 responded to the reagent as the WT. While reduced responses were observed in the mutants containing C136 or C155. Multi-alignment of known mitochondrial carriers, highlighted that only the CAC possesses both Cys residues. This correlates well with the absence of effects of H2S on carriers which does not contain the Cys couple. Conclusions Altogether, these data demonstrate that H2S regulates the CAC by inhibiting or activating transport on the basis of the redox state of the protein. General significance CAC represents a specific target of H2S among mitochondrial carriers in agreement with the presence of a reactive Cys couple.





The etiology of human age-related cataract. Proteins don't last forever

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B

Author(s): Roger J.W. Truscott, Michael G. Friedrich

Background It is probable that the great majority of human cataract results from the spontaneous decomposition of long-lived macromolecules in the human lens. Breakdown/reaction of long-lived proteins is of primary importance and recent proteomic analysis has enabled the identification of the particular crystallins, and their exact sites of amino acid modification. Scope of review Analysis of proteins from cataractous lenses revealed that there are sites on some structural proteins that show a consistently greater degree of deterioration than age-matched normal lenses. Major conclusions The most abundant posttranslational modification of aged lens proteins is racemization. Deamidation, truncation and crosslinking, each arising from the spontaneous breakdown of susceptible amino acids within proteins, are also present. Fundamental to an understanding of nuclear cataract etiology, it is proposed that once a certain degree of modification at key sites occurs, that protein–protein interactions are disrupted and lens opacification ensues. General Significance Since long-lived proteins are now recognized to be present in many other sites of the body, such as the brain, the information gleaned from detailed analyses of degraded proteins from aged lenses will apply more widely to other age-related human diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.





CdTe quantum dots as fluorescent probes to study transferrin receptors in glioblastoma cells

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part A

Author(s): Paulo E. Cabral Filho, Ana L.C. Cardoso, Maria I.A. Pereira, Ana P.M. Ramos, Fernando Hallwass, M. Margarida C.A. Castro, Carlos F.G.C. Geraldes, Beate S. Santos, Maria C. Pedroso de Lima, Giovannia A.L. Pereira, Adriana Fontes







Differential role of arginine mutations on the structure and functions of α-crystallin

Mon, 11/30/2015 - 08:11
Publication date: January 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1860, Issue 1, Part B

Author(s): Alok Kumar Panda, Sandip Kumar Nandi, Ayon Chakraborty, Ram H. Nagaraj, Ashis Biswas

Background α-Crystallin is a major protein of the eye lens in vertebrates. It is composed of two subunits, αA- and αB-crystallin. α-Crystallin is an oligomeric protein having these two subunits in 3:1 ratio. It belongs to small heat shock protein family and exhibits molecular chaperone function, which plays an important role in maintaining the lens transparency. Apart from chaperone function, both subunits also exhibit anti-apoptotic property. Comparison of their primary sequences reveals that αA- and αB-crystallin posses 13 and 14 arginine residues, respectively. Several of them undergo mutations which eventually lead to various eye diseases such as congenital cataract, juvenile cataract, and retinal degeneration. Interestingly, many arginine residues of these subunits are modified during glycation and even some are truncated during aging. All these facts indicate the importance of arginine residues in α-crystallin. Scope of review In this review, we will emphasize the recent in vitro and in vivo findings related to congenital cataract causing arginine mutations in α-crystallin. Major conclusions Congenital cataract causing arginine mutations alters the structure and decreases the chaperone function of α-crystallin. These mutations also affect the lens morphology and phenotypes. Interestingly, non-natural arginine mutations (generated for mimicking the glycation and truncation environment) improve the chaperone function of α-crystallin which may play an important role in maintaining the eye lens transparency during aging. General significance The neutralization of positive charge on the guanidino group of arginine residues is not always detrimental to the functionality of α-crystallin. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.