4w8p

Crystal structure of RIAM TBS1 in complex with talin R7R8 domains

spinqualitylabelsall models 4w8p, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4w8p is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO Gene: Tln1, Tln (LK3 transgenic mice) 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. [AB1IP_MOUSE] Appears to function in the signal transduction from Ras activation to actin cytoskeletal remodeling. Suppresses insulin-induced promoter activities through AP1 and SRE. Mediates Rap1-induced adhesion (By similarity). Publication Abstract from PubMed Plasma membrane (PM)-bound GTPase Rap1 recruits the Rap1-interacting-adaptor-molecule (RIAM), which in turn recruits talin to bind and activate integrins. However, it is unclear how RIAM recruits talin and why its close homolog lamellipodin does not. Here, we report that, although RIAM possesses two talin-binding sites (TBS1 and TBS2), only TBS1 is capable of recruiting cytoplasmic talin to the PM, and the R8 domain is the strongest binding site in talin. Crystal structure of an R7R8:TBS1 complex reveals an unexpected kink in the TBS1 helix that is not shared in the homologous region of lamellipodin. This kinked helix conformation is required for the colocalization of RIAM and talin at the PM and proper activation of integrin. Our findings provide the structural and mechanistic insight into talin recruitment by RIAM that underlies integrin activation and explain the differential functions of the otherwise highly homologous RIAM and lamellipodin in integrin signaling. Structural and Mechanistic Insights into the Recruitment of Talin by RIAM in Integrin Signaling.,Chang YC, Zhang H, Franco-Barraza J, Brennan ML, Patel T, Cukierman E, Wu J Structure. 2014 Dec 2;22(12):1810-20. doi: 10.1016/j.str.2014.09.020. Epub 2014, Nov 20. PMID:25465129 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Talin

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