5fzt
From Proteopedia
The crystal structure of R7R8 in complex with a DLC1 fragment.
Structural highlights
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. [RHG07_HUMAN] Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality.[1] [2] [3] Publication Abstract from PubMedCell migration requires coordination between integrin-mediated cell adhesion to the extracellular matrix and force applied to adhesion sites. Talin plays a key role in coupling integrin receptors to the actomyosin contractile machinery, while deleted in liver cancer 1 (DLC1) is a Rho GAP that binds talin and regulates Rho, and therefore actomyosin contractility. We show that the LD motif of DLC1 forms a helix that binds to the four-helix bundle of the talin R8 domain in a canonical triple-helix arrangement. We demonstrate that the same R8 surface interacts with the paxillin LD1 and LD2 motifs. We identify key charged residues that stabilize the R8 interactions with LD motifs and demonstrate their importance in vitro and in cells. Our results suggest a network of competitive interactions in adhesion complexes that involve LD motifs, and identify mutations that can be used to analyze the biological roles of specific protein-protein interactions in cell migration. LD Motif Recognition by Talin: Structure of the Talin-DLC1 Complex.,Zacharchenko T, Qian X, Goult BT, Jethwa D, Almeida TB, Ballestrem C, Critchley DR, Lowy DR, Barsukov IL Structure. 2016 May 31. pii: S0969-2126(16)30077-6. doi:, 10.1016/j.str.2016.04.016. PMID:27265849[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Mus musculus | Almeida, T | Ballestrem, C | Barsukov, I L | Critchley, D R | Goult, B T | Jethwa, D | Lowy, D R | Qian, X | Zacharchenko, T | Dlc1 | Focal adhesion | Structural protein | Talin
