6r9t

Cryo-EM structure of autoinhibited human talin-1Cryo-EM structure of autoinhibited human talin-1

6r9t, resolution 6.20Å Show:Asymmetric Unit Biological Assembly Structural highlights 6r9t is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: TLN1, KIAA1027, TLN (HUMAN) Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [TLN1_HUMAN] 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 (By similarity). Publication Abstract from PubMed Focal adhesions (FAs) are protein machineries essential for cell adhesion, migration, and differentiation. Talin is an integrin-activating and tension-sensing FA component directly connecting integrins in the plasma membrane with the actomyosin cytoskeleton. To understand how talin function is regulated, we determined a cryoelectron microscopy (cryo-EM) structure of full-length talin1 revealing a two-way mode of autoinhibition. The actin-binding rod domains fold into a 15-nm globular arrangement that is interlocked by the integrin-binding FERM head. In turn, the rod domains R9 and R12 shield access of the FERM domain to integrin and the phospholipid PIP2 at the membrane. This mechanism likely ensures synchronous inhibition of integrin, membrane, and cytoskeleton binding. We also demonstrate that compacted talin1 reversibly unfolds to an approximately 60-nm string-like conformation, revealing interaction sites for vinculin and actin. Our data explain how fast switching between active and inactive conformations of talin could regulate FA turnover, a process critical for cell adhesion and signaling. The Architecture of Talin1 Reveals an Autoinhibition Mechanism.,Dedden D, Schumacher S, Kelley CF, Zacharias M, Biertumpfel C, Fassler R, Mizuno N Cell. 2019 Sep 19;179(1):120-131.e13. doi: 10.1016/j.cell.2019.08.034. PMID:31539492 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Talin