2wp3 | pdb_00002wp3

Crystal structure of the Titin M10-Obscurin like 1 Ig complex

spinqualitylabelsall models 2wp3, resolution 1.48Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wp3 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4 Related: 1tnn, 1ncu, 2j8o, 1bpv, 2cpc, 2j8h, 1nct, 2wwk, 2bk8, 1tiu, 2wwm, 2f8v, 1tit, 2a38, 1tnm, 1waa, 1g1c, 1tki, 1ya5 Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed In the sarcomeric M-band, the giant ruler proteins titin and obscurin, its small homologue obscurin-like-1 (obsl1), and the myosin cross-linking protein myomesin form a ternary complex that is crucial for the function of the M-band as a mechanical link. Mutations in the last titin immunoglobulin (Ig) domain M10, which interacts with the N-terminal Ig-domains of obscurin and obsl1, lead to hereditary muscle diseases. The M10 domain is unusual not only in that it is a frequent target of disease-linked mutations, but also in that it is the only currently known muscle Ig-domain that interacts with two ligands-obscurin and obsl1-in different sarcomeric subregions. Using x-ray crystallography, we show the structural basis for titin M10 interaction with obsl1 in a novel antiparallel Ig-Ig architecture and unravel the molecular basis of titin-M10 linked myopathies. The severity of these pathologies correlates with the disruption of the titin-obsl1/obscurin complex. Conserved signature residues at the interface account for differences in affinity that direct the cellular sorting in cardiomyocytes. By engineering the interface signature residues of obsl1 to obscurin, and vice versa, their affinity for titin can be modulated similar to the native proteins. In single-molecule force-spectroscopy experiments, both complexes yield at forces of around 30 pN, much lower than those observed for the mechanically stable Z-disk complex of titin and telethonin, suggesting why even moderate weakening of the obsl1/obscurin-titin links has severe consequences for normal muscle functions. Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex.,Pernigo S, Fukuzawa A, Bertz M, Holt M, Rief M, Steiner RA, Gautel M Proc Natl Acad Sci U S A. 2010 Feb 1. PMID:20133654 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Obscurin Titin

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