6vgu

Crystal structure of FERM-folded talin head domain bound to the NPLY motif of beta3-integrin

spinqualitylabelsall models 6vgu, resolution 2.78Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vgu is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.78Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TLN1_MOUSE Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts.ITB3_MOUSE Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIB/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIB/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIB/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIB/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surfaces. Fibrinogen binding enhances SELP expression in activated platelets (PubMed:19332769). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and acts as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (By similarity). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (By similarity). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (By similarity). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (By similarity). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (By similarity). ITGAV:ITGB3 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (By similarity). In brain, plays a role in synaptic transmission and plasticity (PubMed:29038237, PubMed:18549786). Involved in the regulation of the serotonin neurotransmission, is required to localize to specific compartments within the synapse the serotonin receptor SLC6A4 and for an appropriate reuptake of serotonin (PubMed:29038237). Controls excitatory synaptic strength by regulating GRIA2-containing AMPAR endocytosis, which affects AMPAR abundance and composition (PubMed:18549786). ITGAV:ITGB3 act as a receptor for CD40LG (By similarity).[UniProtKB:P05106] Publication Abstract from PubMed Binding of the intracellular adapter proteins talin and its cofactor, kindlin, to the integrin receptors induces integrin activation and clustering. These processes are essential for cell adhesion, migration, and organ development. Although the talin head, the integrin-binding segment in talin, possesses a typical FERM-domain sequence, a truncated form has been crystallized in an unexpected, elongated form. This form, however, lacks a C-terminal fragment and possesses reduced beta3-integrin binding. Here, we present a crystal structure of a full-length talin head in complex with the beta3-integrin tail. The structure reveals a compact FERM-like conformation and a tightly associated N-P-L-Y motif of beta3-integrin. A critical C-terminal poly-lysine motif mediates FERM interdomain contacts and assures the tight association with the beta3-integrin cytoplasmic segment. Removal of the poly-lysine motif or disrupting the FERM-folded configuration of the talin head significantly impairs integrin activation and clustering. Therefore, structural characterization of the FERM-folded active talin head provides fundamental understanding of the regulatory mechanism of integrin function. Crystal structure of the FERM-folded talin head reveals the determinants for integrin binding.,Zhang P, Azizi L, Kukkurainen S, Gao T, Baikoghli M, Jacquier MC, Sun Y, Maatta JAE, Cheng RH, Wehrle-Haller B, Hytonen VP, Wu J Proc Natl Acad Sci U S A. 2020 Dec 7. pii: 2014583117. doi:, 10.1073/pnas.2014583117. PMID:33288722 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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