title: Membrane insertion of αA-crystallin is oligomer-size dependent.
abstract: Vertebrate lens is one of the tissues with the highest soluble protein concentration. The predominant soluble proteins in lens fiber cells are crystallins, and among them, α-crystallins belong to the small heat shock protein family with chaperone-like activity. Although α-crystallins are highly soluble in waters, α-crystallins have been detected in the membrane-bound fraction of lens, which will increase in the aged or cataractous lens. In this research, we found αA-crystallin exhibited a complex thermal transition with remarkable changes in secondary and quaternary structures. Treatment of αA-crystallin at high temperatures induced larger oliogomers with higher hydrophobic exposure. Both heat-treated and untreated αA-crystallin could insert into lipid monolayer directly as revealed by monolayer surface pressure experiments. Heat-treatment facilitated the membrane insertion of αA-crystallin and increased the membrane-bound fraction in the cells. The membrane-binding ability of αA-crystallin could be altered by cataract-causing mutations R116C, R116H and Y118D. Our results suggested that the irreversible changes in oligomer size induced by various stresses might promote the membrane association of αA-crystallin and therefore might play a role in aged cataract. Alternations in the membrane binding ability of α-crystallins might be important to the understanding of both aged and congenital cataracts.
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Harry Christianto
authors.initials: HC
authors.lastname: Tjondro
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yi-Bo
authors.initials: YB
authors.lastname: Xi
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jing-Tan
authors.initials: JT
authors.lastname: Su
authors.affiliation: State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: ybyan@tsinghua.edu.cn.
authors.forename: Yong-Bin
authors.initials: YB
authors.lastname: Yan
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D002386:Cataract / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry*; D002845:Chromatography; D003459:Crystallins / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008856:Microscopy, Fluorescence; D009154:Mutation; D010718:Phosphatidylserines / Q000737:chemistry; D011312:Pressure; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013696:Temperature
chemical_list: C511246:CRYAA protein, human; D003459:Crystallins; D018076:DNA, Complementary; D006360:Heat-Shock Proteins; D008055:Lipids; D010718:Phosphatidylserines; D015060:1,2-Dipalmitoylphosphatidylcholine; D012710:Serum Albumin, Bovine; C038694:dipalmitoylphosphatidylserine
keywords: Cataract; Heat shock; Membrane binding; Oligomerization; Small heat shock proteins; αA-crystallin