2jtd
Skelemin Immunoglobulin C2 like domain 4Skelemin Immunoglobulin C2 like domain 4
Structural highlights
FunctionMYOM1_MOUSE May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle. May also contact myosin filaments. Also binds beta-integrins. 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 PubMedSkelemin is a large cytoskeletal protein critical for cell morphology. Previous studies have suggested that its two-tandem immunoglobulin C2-like repeats (SkIgC4 and SkIgC5) are involved in binding to integrin beta3 cytoplasmic tail (CT), providing a mechanism for skelemin to regulate integrin-mediated signaling and cell spreading. Using NMR spectroscopy, we have studied the molecular details of the skelemin IgC45 interaction with the cytoplasmic face of integrin alphaIIbbeta3. Here, we show that skelemin IgC45 domains form a complex not only with integrin beta3 CT but also, surprisingly, with the integrin alphaIIb CT. Chemical shift mapping experiments demonstrate that both membrane-proximal regions of alphaIIb and beta3 CTs are involved in binding to skelemin. NMR structural determinations, combined with homology modeling, revealed that SkIgC4 and SkIgC5 both exhibited a conserved Ig-fold and both repeats were required for effective binding to and attenuation of alphaIIbbeta3 cytoplasmic complex. These data provide the first molecular insight into how skelemin may interact with integrins and regulate integrin-mediated signaling and cell spreading. Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin.,Deshmukh L, Tyukhtenko S, Liu J, Fox JE, Qin J, Vinogradova O J Biol Chem. 2007 Nov 2;282(44):32349-56. Epub 2007 Sep 5. PMID:17804417[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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