Human skeletal muscle nebulin sequence encodes a blueprint for thin filament architecture: Sequence motifs and affinity profiles of tandem repeats and terminal SH3

Kuan Wang, Marie Knipfer, Qi Quan Huang, Ann Van Heerden, Lillian Chi Li Hsu, Gustavo Gutierrez, Xiao Lan Quian, Hansel Stedman

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Analysis of deduced protein sequence and structural motifs of ∼5500 residues of human fetal skeletal muscle nebulin reveals the design principles of this giant multifunctional protein in the sarcomere. The bulk of the sequence is constructed of ∼150 tandem copies of ∼35-residue modules that can be classified into seven types. The majority of these modules form 20 super-repeats, with each super-repeat containing a 7-module set (one of each type in the same order). These super-repeats are further divided into eight segments: with six segments containing adjacent, highly homologous super-repeats, one single repeat segment consisting of 8 nebulin modules of the same type, and a non-repeat segment terminating with a SH3 domain at the C terminus. The interactions of actin, tropomyosin, troponin, and calmodulin with nebulin fragments consisting of either repeating modules or the SH3 domain support its role as a giant actin-binding cofilament of the composite thin filament. Such affinity profiles also suggest that nebulin may bind to tropomyosin and troponin to form a composite calcium-linked regulatory complex on the thin filament. The modular construction, super-repeat structure, and segmental organization of nebulin sequence appear to encode thin filament length, periodicity, insertion, and sarcomere proportion in the resting muscle.

Original languageEnglish
Pages (from-to)4304-4314
Number of pages11
JournalJournal of Biological Chemistry
Volume271
Issue number8
DOIs
Publication statusPublished - Feb 23 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Human skeletal muscle nebulin sequence encodes a blueprint for thin filament architecture: Sequence motifs and affinity profiles of tandem repeats and terminal SH3'. Together they form a unique fingerprint.

  • Cite this