title: Differential role of arginine mutations on the structure and functions of α-crystallin.
abstract: 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.
  
  
  METHODS
  In this review, we will emphasize the recent in vitro and in vivo findings related to congenital cataract causing arginine mutations in α-crystallin.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, Odisha 751013, India.
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Panda
authors.affiliation: School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, Odisha 751013, India.
authors.forename: Sandip Kumar
authors.initials: SK
authors.lastname: Nandi
authors.affiliation: School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, Odisha 751013, India.
authors.forename: Ayon
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Ram H
authors.initials: RH
authors.lastname: Nagaraj
authors.affiliation: School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Bhubaneswar, Odisha 751013, India. Electronic address: abiswas@iitbbs.ac.in.
authors.forename: Ashis
authors.initials: A
authors.lastname: Biswas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000235:genetics* / Q000378:metabolism; D003459:Crystallins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D013329:Structure-Activity Relationship; D038203:alpha-Crystallin B Chain / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D038201:alpha-Crystallins / Q000737:chemistry / Q000235:genetics / Q000502:physiology
chemical_list: C511246:CRYAA protein, human; C059215:CRYAB protein, human; D003459:Crystallins; D038203:alpha-Crystallin B Chain; D038201:alpha-Crystallins; D001120:Arginine
keywords: Arginine mutations; Chaperone; Congenital cataract; Post-translational modifications; α-Crystallin