Interaction of nebulin SH3 domain with titin PEVK and myopalladin: implications for the signaling and assembly role of titin and nebulin

FEBS Letters

Ma, Kan¹  Wang, Kuan¹ 

[1] Muscle Proteomics and Nanotechnology Section, Laboratory of Muscle Biology, B50/Rm 1140, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Circular dichroism;    Nuclear magnetic resonance;    Fluorescence;    SH3 domain of nebulin;    Myopalladin;    PEVK;    HSQC;    heteronuclear single quantum coherence;    MyoP1;    MyoP2;    MyoP3;    peptide fragments of myopalladin;    MALDI-TOF;    matrix-assisted laser desorption ionization time of flight;    PPII;    polyproline type II left-handed helix;    PR;    a 28-mer sequence module of PEVK;    PR1;    PR2;    PR3;    subfragments of PR;    Sos;    SH3 binding sequence of guanine nucleotide exchange factor;   

DOI  :  10.1016/S0014-5793(02)03655-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Skeletal muscle nebulin is thought to determine thin filament length and regulate actomyosin interaction in a calcium/calmodulin or S100 sensitive manner. We have investigated the binding of nebulin SH3 with proline-rich peptides derived from the 28-mer PEVK modules of titin and the Z-line protein myopalladin, using fluorescence, circular dichroism and nuclear magnetic resonance techniques. Of the six peptides studied, PR2 of titin (VPEKKAPVAPPK) and myopalladin MyoP2 (⁶⁴⁶VKEPPPVLAKPK⁶⁵⁷) bind to nebulin SH3 with micromolar affinity (∼31 and 3.4 μM, respectively), whereas the other four peptides bind weakly (>100 μM). Sequence analysis of titins reveals numerous SH3 binding motifs that are highly enriched in the PEVK segments of titin isoforms. Our findings suggest that titin PEVK and myopalladin may play signaling roles in targeting and orientating nebulin to the Z-line during sarcomere assembly.

【 授权许可】

Unknown