1LDS

Crystal Structure of monomeric human beta-2-microglobulin

Summary for 1LDS

• Entry DOI: 10.2210/pdb1lds/pdb
• Related: 1DUZ
• Descriptor: beta-2-microglobulin, SODIUM ION (3 entities in total)
• Functional Keywords: immunoglobulin constant domain, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P61769
• Total number of polymer chains: 1
• Total formula weight: 11902.35

Authors

Trinh, C.H.,Smith, D.P.,Kalverda, A.P.,Phillips, S.E.V.,Radford, S.E. (deposition date: 2002-04-09, release date: 2002-07-31, Last modification date: 2023-09-20)

Primary citation

Trinh, C.H.,Smith, D.P.,Kalverda, A.P.,Phillips, S.E.,Radford, S.E.
Crystal structure of monomeric human beta-2-microglobulin reveals clues to its amyloidogenic properties.
Proc.Natl.Acad.Sci.USA, 99:9771-9776, 2002

PubMed Abstract: Dissociation of human beta-2-microglobulin (beta(2)m) from the heavy chain of the class I HLA complex is a critical first step in the formation of amyloid fibrils from this protein. As a consequence of renal failure, the concentration of circulating monomeric beta(2)m increases, ultimately leading to deposition of the protein into amyloid fibrils and development of the disorder, dialysis-related amyloidosis. Here we present the crystal structure of a monomeric form of human beta(2)m determined at 1.8-A resolution that reveals remarkable structural changes relative to the HLA-bound protein. These involve the restructuring of a beta bulge that separates two short beta strands to form a new six-residue beta strand at one edge of this beta sandwich protein. These structural changes remove key features proposed to have evolved to protect beta sheet proteins from aggregation [Richardson, J. & Richardson, D. (2002) Proc. Natl. Acad. Sci. USA 99, 2754-2759] and replaces them with an aggregation-competent surface. In combination with solution studies using (1)H NMR, we show that the crystal structure presented here represents a rare species in solution that could provide important clues about the mechanism of amyloid formation from the normally highly soluble native protein.

PubMed: 12119416
DOI: 10.1073/pnas.152337399

Experimental method

X-RAY DIFFRACTION (1.8 Å)