3tm6

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

spinqualitylabelsall models 3tm6, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tm6 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: PEG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease B2MG_HUMAN Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation. Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis. Function B2MG_HUMAN Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed beta-2 microglobulin (beta2m) is an amyloidogenic protein responsible for dialysis-related amyloidosis in man. In the early stages of amyloid fibril formation, beta2m 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 beta2m 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 beta2m 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 beta2m D-strands and is conserved. Notably, DIMC20 and DIMC50 trigger amyloid formation in wild-type beta2m 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 beta2m. Implications for beta2m oligomerization are discussed. A recurrent D-strand association interface is observed in beta-2 microglobulin oligomers.,Colombo M, de Rosa M, Bellotti V, Ricagno S, Bolognesi M FEBS J. 2012 Mar;279(6):1131-43. doi: 10.1111/j.1742-4658.2012.08510.x. Epub 2012, Feb 23. PMID:22289140 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures

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