4z8g
Chimera of Tropomodulin-1 and Leiomodin-1 Actin-Binding Site 2 (TL1 ABS2)Chimera of Tropomodulin-1 and Leiomodin-1 Actin-Binding Site 2 (TL1 ABS2)
Structural highlights
FunctionLMOD1_HUMAN TMOD1_HUMAN Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton. May play an important role in regulating the organization of actin filaments by preferentially binding to a specific tropomyosin isoform at its N-terminus.[1] Publication Abstract from PubMedHow proteins sharing a common fold have evolved different functions is a fundamental question in biology. Tropomodulins (Tmods) are prototypical actin filament pointed-end-capping proteins, whereas their homologues, Leiomodins (Lmods), are powerful filament nucleators. We show that Tmods and Lmods do not compete biochemically, and display similar but distinct localization in sarcomeres. Changes along the polypeptide chains of Tmods and Lmods exquisitely adapt their functions for capping versus nucleation. Tmods have alternating tropomyosin (TM)- and actin-binding sites (TMBS1, ABS1, TMBS2 and ABS2). Lmods additionally contain a C-terminal extension featuring an actin-binding WH2 domain. Unexpectedly, the different activities of Tmods and Lmods do not arise from the Lmod-specific extension. Instead, nucleation by Lmods depends on two major adaptations-the loss of pointed-end-capping elements present in Tmods and the specialization of the highly conserved ABS2 for recruitment of two or more actin subunits. The WH2 domain plays only an auxiliary role in nucleation. How Leiomodin and Tropomodulin use a common fold for different actin assembly functions.,Boczkowska M, Rebowski G, Kremneva E, Lappalainen P, Dominguez R Nat Commun. 2015 Sep 15;6:8314. doi: 10.1038/ncomms9314. PMID:26370058[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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