1SHM

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

Summary for 1SHM

• Entry DOI: 10.2210/pdb1shm/pdb
• Related: 1f2x 1HCV 1MEL
• Descriptor: ANTIBODY RIG (2 entities in total)
• Functional Keywords: heavy chain variable domain, vhh domain, immunoglobulin, immune system
• Biological source: Lama glama (llama)
• Total number of polymer chains: 4
• Total formula weight: 54720.62

Authors

Bond, C.J.,Wiesmann, C.,Marsters, J.C.,Sidhu, S.S. (deposition date: 2004-02-26, release date: 2005-03-08, Last modification date: 2024-11-06)

Primary citation

Bond, C.J.,Wiesmann, C.,Marsters, J.C.,Sidhu, S.S.
A structure-based database of antibody variable domain diversity.
J.Mol.Biol., 348:699-709, 2005

PubMed Abstract: 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.

PubMed: 15826665
DOI: 10.1016/j.jmb.2005.02.063

Experimental method

X-RAY DIFFRACTION (1.9 Å)