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Crystal structures of truncated alphaA and alphaB crystallins reveal structural mechanisms of polydispersity important for eye lens function
Author(s) -
Laganowsky Arthur,
Benesch Justin L. P.,
Landau Meytal,
Ding Linlin,
Sawaya Michael R.,
Cascio Duilio,
Huang Qingling,
Robinson Carol V.,
Horwitz Joseph,
Eisenberg David
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.380
Subject(s) - crystallin , dispersity , crystallization , crystallography , biophysics , chaperone (clinical) , chemistry , stereochemistry , materials science , biochemistry , biology , polymer chemistry , medicine , organic chemistry , pathology
Small heat shock proteins alphaA and alphaB crystallin form highly polydisperse oligomers that frustrate protein aggregation, crystallization, and amyloid formation. Here, we present the crystal structures of truncated forms of bovine alphaA crystallin (AAC 59–163 ) and human alphaB crystallin (ABC 68–162 ), both containing the C‐terminal extension that functions in chaperone action and oligomeric assembly. In both structures, the C‐terminal extensions swap into neighboring molecules, creating runaway domain swaps. This interface, termed DS, enables crystallin polydispersity because the C‐terminal extension is palindromic and thereby allows the formation of equivalent residue interactions in both directions. That is, we observe that the extension binds in opposite directions at the DS interfaces of AAC 59–163 and ABC 68–162 . A second dimeric interface, termed AP, also enables polydispersity by forming an antiparallel beta sheet with three distinct registration shifts. These two polymorphic interfaces enforce polydispersity of alpha crystallin. This evolved polydispersity suggests molecular mechanisms for chaperone action and for prevention of crystallization, both necessary for transparency of eye lenses.