3TM6

Crystal structure of the beta-2 microglobulin DIMC50 disulphide-linked homodimer mutant

Summary for 3TM6

• Entry DOI: 10.2210/pdb3tm6/pdb
• Related: 2X89 3CIQ
• Descriptor: Beta-2-microglobulin, DI(HYDROXYETHYL)ETHER, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: immunoglobulin-like fold, mhc class i, light chain, immune system
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P61769
• Total number of polymer chains: 8
• Total formula weight: 95927.51

Authors

Colombo, M.,Ricagno, S.,Bolognesi, M. (deposition date: 2011-08-31, release date: 2012-09-05, Last modification date: 2024-11-06)

Primary citation

Colombo, M.,de Rosa, M.,Bellotti, V.,Ricagno, S.,Bolognesi, M.
A recurrent D-strand association interface is observed in beta-2 microglobulin oligomers.
Febs J., 279:1131-1143, 2012

PubMed Abstract: β-2 microglobulin (β2m) is an amyloidogenic protein responsible for dialysis-related amyloidosis in man. In the early stages of amyloid fibril formation, β2m associates into dimers and higher oligomers, although the structural details of such aggregates are poorly understood. To characterize the protein-protein interactions supporting the formation of oligomers, three individual β2m cysteine mutants and their disulfide-linked homodimers (DIMC20, DIMC50 and DIMC60) were prepared. Amyloid propensity, oligomerization state in solution and crystallogenesis were tested for each β2m homodimer: DIMC20 and DIMC50 display a mixture of tetrameric and dimeric species in solution and also yield protein crystals and amyloid fibrils, whereas DIMC60 is dimeric in solution but does not form protein crystals nor amyloid fibrils. The X-ray structures of DIMC20 and DIMC50 show that the two engineered dimers form a tetrameric assembly; for both tetrameric species, the noncovalent association interface is based on the interaction of facing β2m D-strands and is conserved. Notably, DIMC20 and DIMC50 trigger amyloid formation in wild-type β2m in unseeded reactions. Thus, when the D-D-strand interface is impaired by an intermolecular disulfide bond (as in DIMC60), the formation of tetramers is hindered, and the protein is not amyloidogenic and does not promote amyloid aggregation of wild-type β2m. Implications for β2m oligomerization are discussed.

PubMed: 22289140
DOI: 10.1111/j.1742-4658.2012.08510.x

Experimental method

X-RAY DIFFRACTION (2.7 Å)