1shm

Convergent solutions to VHH domain stabilization from natural and in vitro evolution

spinqualitylabelsall models 1shm, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1shm is a 4 chain structure with sequence from Camelus glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1hcv, 1mel, 1f2x Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The diversity of natural antibodies is limited by the genetic mechanisms that engender diversity and the functional requirements of antigen binding. Using an in vitro-evolved autonomous heavy chain variable domain (V(H)H-RIG), we have investigated the limits of structurally-tolerated diversity in the three complementarity-determining regions and a fourth loop within the third framework region. We determined the X-ray crystal structure of the V(H)H-RIG domain at 1.9A resolution and used it to guide the design of phage-displayed libraries encompassing the four loops. The libraries were subjected to selections for structural stability, and a database of structurally-tolerated sequences was compiled from the sequences of approximately 1000 unique clones. The results reveal that all four loops accommodate significantly greater diversity than is observed in nature. Thus, it appears that most sequence biases in the natural immune repertoire arise from factors other than structural constraints and, consequently, it should be possible to enhance the functions of antibodies significantly through in vitro evolution. A structure-based database of antibody variable domain diversity.,Bond CJ, Wiesmann C, Marsters JC Jr, Sidhu SS J Mol Biol. 2005 May 6;348(3):699-709. PMID:15826665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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