2JTD

Skelemin Immunoglobulin C2 like domain 4

Summary for 2JTD

• Entry DOI: 10.2210/pdb2jtd/pdb
• Descriptor: Myomesin-1 (1 entity in total)
• Functional Keywords: skelemin, immunoglobulin domain, muscle protein, thick filament, immune system, cell adhesion
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 1
• Total formula weight: 16397.60

Authors

Deshmukh, L.,Vinogradova, O. (deposition date: 2007-07-27, release date: 2007-09-04, Last modification date: 2024-05-29)

Primary citation

Deshmukh, L.,Tyukhtenko, S.,Liu, J.,Fox, J.E.,Qin, J.,Vinogradova, O.
Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin.
J.Biol.Chem., 282:32349-32356, 2007

PubMed Abstract: Skelemin 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.

PubMed: 17804417
DOI: 10.1074/jbc.M704666200

Experimental method

SOLUTION NMR