3qd6
From Proteopedia
Crystal structure of the CD40 and CD154 (CD40L) complex
Structural highlights
DiseaseTNR5_HUMAN Defects in CD40 are the cause of immunodeficiency with hyper-IgM type 3 (HIGM3) [MIM:606843. A rare immunodeficiency syndrome characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE. It results in a profound susceptibility to bacterial infections.[1] FunctionTNR5_HUMAN Receptor for TNFSF5/CD40LG. Publication Abstract from PubMedCD40 is a tumor necrosis factor receptor (TNFR) family protein that plays an important role in B cell development. CD154/CD40L is the physiological ligand of CD40. We have determined the crystal structure of the CD40-CD154 complex at 3.5 A resolution. The binding site of CD40 is located in a crevice formed between two CD154 subunits. Charge complementarity plays a critical role in the CD40-CD154 interaction. Some of the missense mutations found in hereditary hyper-IgM syndrome can be mapped to the CD40-CD154 interface. The CD40 interaction area of one of the CD154 subunits is twice as large as that of the other subunit forming the binding crevice. This is because cysteine-rich domain 3 (CRD3) of CD40 has a disulfide bridge in an unusual position that alters the direction of the ladder-like structure of CD40. The Ser(132) loop of CD154 is not involved in CD40 binding but its substitution significantly reduces p38- and ERK-dependent signaling by CD40, whereas JNK-dependent signaling is not affected. These findings suggest that ligand-induced di- or trimerization is necessary but not sufficient for complete activation of CD40. Crystallographic and mutational analysis of the CD40-CD154 complex and its implications for receptor activation.,An HJ, Kim YJ, Song DH, Park BS, Kim HM, Lee JD, Paik SG, Lee JO, Lee H J Biol Chem. 2011 Apr 1;286(13):11226-35. Epub 2011 Feb 1. PMID:21285457[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Kim HM | Kim YJ | Lee J-O | Park BS | Song DH