3CIQ

A regulatable switch mediates self-association in an immunoglobulin fold

Summary for 3CIQ

• Entry DOI: 10.2210/pdb3ciq/pdb
• Related: 2f8o
• Descriptor: Beta-2-microglobulin, COPPER (II) ION, L(+)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: class-1 mhc, amyloid, protein folding, dialysis-related amyloidosis, beta-2 microglobulin, disease mutation, glycation, glycoprotein, immune response, immunoglobulin domain, mhc i, pyrrolidone carboxylic acid, secreted, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P61769
• Total number of polymer chains: 12
• Total formula weight: 143573.23

Authors

Calabrese, M.F.,Eakin, C.M.,Wang, J.M.,Miranker, A.D. (deposition date: 2008-03-11, release date: 2008-09-02, Last modification date: 2024-11-06)

Primary citation

Calabrese, M.F.,Eakin, C.M.,Wang, J.M.,Miranker, A.D.
A regulatable switch mediates self-association in an immunoglobulin fold.
Nat.Struct.Mol.Biol., 15:965-971, 2008

PubMed Abstract: Beta-2 microglobulin (beta2m) is a globular protein that self-associates into fibrillar amyloid deposits in patients undergoing hemodialysis therapy. Formation of these beta-sheet-rich assemblies is a fundamental property of polypeptides that can be triggered by diverse conditions. For beta2m, oligomerization into pre-amyloidogenic states occurs in specific response to coordination by Cu2+. Here we report the basis for this self-association at atomic resolution. Metal is not a direct participant in the molecular interface. Rather, binding results in distal alterations enabling the formation of two new surfaces. These interact to form a closed hexameric species. The origins of this include isomerization of a buried and conserved cis-proline previously implicated in the beta2m aggregation pathway. The consequences of this isomerization are evident and reveal a molecular basis for the conversion of this robust monomeric protein into an amyloid-competent state.

PubMed: 19172750

Experimental method

X-RAY DIFFRACTION (2.9 Å)