PDBsum entry 3l1e

Chaperone

PDB id: 3l1e

Contents

Protein chain

105 a.a.

Ligands

GOL

Metals

_ZN

Waters ×95

References listed in PDB file

Key reference

• Title: Crystal structures of truncated alphaa and alphab crystallins reveal structural mechanisms of polydispersity important for eye lens function.
• Authors: A.Laganowsky, J.L.Benesch, M.Landau, L.Ding, M.R.Sawaya, D.Cascio, Q.Huang, C.V.Robinson, J.Horwitz, D.Eisenberg.
• Ref.: Protein Sci, 2010, 19, 1031-1043.
• PubMed id: 20440841

Abstract

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.