3u59
N-terminal 98-aa fragment of smooth muscle tropomyosin betaN-terminal 98-aa fragment of smooth muscle tropomyosin beta
Structural highlights
Function[TPM2_CHICK] Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. Publication Abstract from PubMedA large number of tropomyosin (Tm) isoforms function as gatekeepers of the actin filament, controlling the spatiotemporal access of actin-binding proteins to specialized actin networks. Residues approximately 40-80 vary significantly among Tm isoforms, but the impact of sequence variation on Tm structure and interactions with actin is poorly understood, because structural studies have focused on skeletal muscle Tmalpha. We describe structures of N-terminal fragments of smooth muscle Tmalpha and Tmbeta (sm-Tmalpha and sm-Tmbeta). The 2.0-A structure of sm-Tmalpha81 (81-aa) resembles that of skeletal Tmalpha, displaying a similar super-helical twist matching the contours of the actin filament. The 1.8-A structure of sm-Tmalpha98 (98-aa) unexpectedly reveals an antiparallel coiled coil, with the two chains staggered by only 4 amino acids and displaying hydrophobic core interactions similar to those of the parallel dimer. In contrast, the 2.5-A structure of sm-Tmbeta98, containing Gly-Ala-Ser at the N terminus to mimic acetylation, reveals a parallel coiled coil. None of the structures contains coiled-coil stabilizing elements, favoring the formation of head-to-tail overlap complexes in four of five crystallographically independent parallel dimers. These complexes show similarly arranged 4-helix bundles stabilized by hydrophobic interactions, but the extent of the overlap varies between sm-Tmbeta98 and sm-Tmalpha81 from 2 to 3 helical turns. The formation of overlap complexes thus appears to be an intrinsic property of the Tm coiled coil, with the specific nature of hydrophobic contacts determining the extent of the overlap. Overall, the results suggest that sequence variation among Tm isoforms has a limited effect on actin binding but could determine its gatekeeper function. Structural analysis of smooth muscle tropomyosin alpha and beta isoforms.,Rao JN, Rivera-Santiago R, Li XE, Lehman W, Dominguez R J Biol Chem. 2012 Jan 27;287(5):3165-74. Epub 2011 Nov 27. PMID:22119916[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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