Each actin subunit has three nebulin binding sites: Implications for steric blocking

Natalya Lukoyanova, Margaret S. VanLoock, Albina Orlova, Vitold E. Galkin, Kuan Wang, Edward H. Egelman

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Nebulin is a giant protein that spans most of the muscle thin filament [1, 2]. Mutations in nebulin result in myopathies and dystrophies [3, 4]. Nebulin contains ∼200 copies of ∼35 residue modules, each believed to contain an actin binding site, organized into seven-module superrepeats [5, 6]. The strong correlation between the number of nebulin modules and the length of skeletal muscle thin filaments in different species suggests that nebulin determines thin filament length [2, 7, 8]. Little information exists about the interactions between intact nebulin and F-actin. More insight has come from working with fragments of nebulin, containing from one to hundreds of actin binding modules. However, the observed stoichiometry of binding between these fragments and actin has ranged from 0.4 to 13 modules per actin subunit [9-12]. We have used electron microscopy and a novel method of helical image analysis to characterize complexes of F-actin with a nebulin fragment. The fragment binds as an extended structure spanning three actin subunits and binding to different sites on each actin. Muscle regulation involves tropomyosin movement on the surface of actin, with binding in three states. Our results suggest the intriguing possibility that intact nebulin may also be able to occupy three different sites on F-actin.

Original languageEnglish
Pages (from-to)383-388
Number of pages6
JournalCurrent Biology
Volume12
Issue number5
DOIs
Publication statusPublished - Mar 5 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Lukoyanova, N., VanLoock, M. S., Orlova, A., Galkin, V. E., Wang, K., & Egelman, E. H. (2002). Each actin subunit has three nebulin binding sites: Implications for steric blocking. Current Biology, 12(5), 383-388. https://doi.org/10.1016/S0960-9822(02)00678-4