6ek2
From Proteopedia
CRYSTAL STRUCTURE OF HUMAN CD81 LARGE EXTRACELLULAR LOOP IN COMPLEX WITH SINGLE CHAIN FV FRAGMENT 10
Structural highlights
DiseaseCD81_HUMAN Defects in CD81 are the cause of immunodeficiency common variable type 6 (CVID6) [MIM:613496; also called antibody deficiency due to CD81 defect. CVID6 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.[1] FunctionCD81_HUMAN May play an important role in the regulation of lymphoma cell growth. Interacts with a 16-kDa Leu-13 protein to form a complex possibly involved in signal transduction. May act as the viral receptor for HCV. Publication Abstract from PubMedHepatitis C viral infection is the major cause of chronic hepatitis that affects as many as 71 million people worldwide. Rather than target the rapidly shifting viruses and their numerous serotypes, four independent antibodies were made to target the host antigen CD81 and were shown to block hepatitis C viral entry. The single-chain variable fragment of each antibody was crystallized in complex with the CD81 large extracellular loop in order to guide affinity maturation of two distinct antibodies by phage display. Affinity maturation of antibodies using phage display has proven to be critical to therapeutic antibody development and typically involves modification of the paratope for increased affinity, improved specificity, enhanced stability or a combination of these traits. One antibody was engineered for increased affinity for human CD81 large extracellular loop that equated to increased efficacy, while the second antibody was engineered for cross-reactivity with cynomolgus CD81 to facilitate animal model testing. The use of structures to guide affinity maturation library design demonstrates the utility of combining structural analysis with phage display technologies. Structure-Guided Combinatorial Engineering Facilitates Affinity and Specificity Optimization of Anti-CD81 Antibodies.,Nelson B, Adams J, Kuglstatter A, Li Z, Harris SF, Liu Y, Bohini S, Ma H, Klumpp K, Gao J, Sidhu SS J Mol Biol. 2018 May 17. pii: S0022-2836(18)30434-0. doi:, 10.1016/j.jmb.2018.05.018. PMID:29778602[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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