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From Proteopedia
Cryo-EM structure of human integrin alpha-E beta-7
Structural highlights
FunctionITB7_HUMAN Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alpha-4/beta-7 interacts with the cell surface adhesion molecules MADCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and fibronectin, an extracellular matrix component. It recognizes one or more domains within the alternatively spliced CS-1 region of fibronectin. Interactions involves the tripeptide L-D-T in MADCAM1, and L-D-V in fibronectin. Binds to HIV-1 gp120, thereby allowing the virus to enter GALT, which is thought to be the major trigger of AIDS disease. Interaction would involve a tripeptide L-D-I in HIV-1 gp120. Integrin alpha-E/beta-7 (HML-1) is a receptor for E-cadherin. Publication Abstract from PubMedThe integrin family is a transmembrane receptor that plays critical roles in the cell-cell and cell-extracellular matrix adhesion, signal transduction such as cell cycle regulation, organization of the intracellular cytoskeleton, and immune responses. Consequently, dysfunction of integrins is associated with a wide range of human diseases, including cancer and immune diseases, which makes integrins therapeutic targets for drug discovery. Here we report the cryo-EM structure of the human alpha-I domain-containing full-length integrin alphaEbeta7, which is expressed in the leukocytes of the immune system and a drug target for inflammatory bowel disease (IBD). The structure reveals the half-bent conformation, an intermediate between the close and the open conformation, while the alpha-I domain responsible for the ligand binding covers the headpiece domain by a unique spatial arrangement. Our results provide the structural information for the drug design targeting IBD. Cryo-EM structure of I domain-containing integrin alphaEbeta7.,Akasaka H, Sato D, Shihoya W, Nureki O, Kise Y Biochem Biophys Res Commun. 2024 May 14;721:150121. doi: , 10.1016/j.bbrc.2024.150121. PMID:38781659[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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