PDBsum entry 2jtd

Cell adhesion

PDB id: 2jtd

Contents

Protein chain

122 a.a. *

* Residue conservation analysis

PDB id:

2jtd

Name:

Cell adhesion

Title:

Skelemin immunoglobulin c2 like domain 4

Structure:

Myomesin-1. Chain: a. Fragment: residues:1207-1328. Synonym: skelemin. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: myom1. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

L.Deshmukh,O.Vinogradova

Key ref:

L.Deshmukh et al. (2007). Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin. J Biol Chem, 282, 32349-32356. PubMed id: 17804417 DOI: 10.1074/jbc.M704666200

Date:

27-Jul-07 Release date: 04-Sep-07

Protein chain

Q62234  (MYOM1_MOUSE) -  Myomesin-1 from Mus musculus

Seq: 1667 a.a.

Struc: 122 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M704666200

J Biol Chem 282:32349-32356 (2007)

PubMed id: 17804417

Structural insight into the interaction between platelet integrin alphaIIbbeta3 and cytoskeletal protein skelemin.

L.Deshmukh, S.Tyukhtenko, J.Liu, J.E.Fox, J.Qin, O.Vinogradova.

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.

Selected figure(s)

Figure 1.
Composition of skelemin.A, skelemin contains one unique region, one serine/proline-rich region, seven Ig-C2-like and five FN-like domains. SkIgC4 and SkIgC5 domains, squared in this figure, have been implicated in integrin binding. B, primary sequences and alignment of skelemin Ig-C2 domains 4 and 5.

Figure 2.
Summary of the spectral perturbations for integrin β[3]/skelemin and α[IIb]/skelemin interactions. All experiments were performed in 0.25× PBS (pH 6.2) buffer at 25 °C. A, expanded region of HSQC spectra of ^15N-labeled β[3] tail in the absence (black) and presence of the unlabeled skelemin IgC45 at different ratios: 1:1, green; 1:3, red; 1:5, blue. Residues labeled indicate the most significant changes. B, chemical shift changes of the β[3] tail upon SkIgC45 binding. Bars are colored according to the different ratios as presented in A. First nine residues (Lys^716-Arg^724) in 1:5 (blue) series are undetectable because of extreme line-broadening and are shown as bars with maximum values. C, chemical shift changes of the β[3] tail upon binding to different skelemin constructs at the ratio of 1:3. Bars are colored according to the interaction with a particular domain of skelemin: green bars, interaction with SkIgC4; blue bars, interaction with SkIgC5; red bars, interaction with SkIgC45. The last bar in each series represents chemical shifts of the Trp^739 side-chain HN; His^722 is undetectable (probably because of the exchange with water) and is not shown in green and blue series. Δδ(HN,N) in ppm refers to the combined HN and N chemical shift changes, according to the equation: Δδ(HN,N) = ((Δδ[HN]^2 + 0.2 (Δδ[N])^2)[½], where Δδ = δ[bound] - δ[free]. D, HSQC spectra of ^15N/^2H-labeled skelemin IgC45 in the absence (black) and presence (red) of the unlabeled β[3] tail. E, HSQC spectra of ^15N-labeled α[IIb] in the absence (black) or presence (red) of unlabeled SkIgC45 at the ratio of 1:5.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 32349-32356) copyright 2007.

Figures were selected by an automated process.