Assemblases and coupling proteins in thick filament assembly

Feizhou Liu, Jose M. Barral, Christopher C. Bauer, Irving Ortiz, Richard G. Cook, Michael F. Schmied, Henry F. Epstein

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Thick filaments are stable assemblies of myosin that are characteristic of specific muscle types from both vertebrates and invertebrates. In general, their structure and assembly require remarkably precise determination of lengths and diameters, structural differentiation and nonequivalence of myosins, a high degree of inelasticity and rigidity, and dynamic regulation of assembly and disassembly in response to both extracellular and intracellular signals. Directed assembly of myosin in which additional proteins function in key roles, therefore, is more likely to be significant than the simple self assembly of myosin into thick filaments. The nematode Caenorhabditis elegans permits a wide spectrum of biochemical, genetic, molecular and structural approaches to be applied to the experimental testing of this hypothesis. Biochemical analysis of C. elegans thick filaments reveals that paramyosin, a homologue of the myosin rod that is the unique product of a single genetic locus, exists as two populations which differ by post-translational modification. The major paramyosin species interacts with the two genetically specified myosin heavy chain isoforms. The minor paramyosin species is organized within the cores of the thick filaments, where it is associated stoichiometrically with three recently identified proteins P20, P28 and P30. These proteins have now been characterized molecularly and contain unique, novel amino acid sequences. Structural analysis of the core shows that seven paramyosin subfilaments are crosslinked by additional internal proteins into a highly rigid tubule. P20, P28 and P30 are proposed to couple the paramyosin subfilaments together into the core tubule during filament assembly. Mutants that affect paramyosin assembly are being characterized for alterations in the core proteins. A fourth protein has been identified recently as the product of the unc-45 gene. Computational analysis of this gene's DNA suggests that the predicted protein may exhibit protein phosphatase and chaperone activities. Genetic analysis shows that three classes of specific unc-45 mutant proteins differentially interact with the two myosins during thick filament assembly. The unc-45 protein is proposed to be a myosin assemblase, a protein catalyst of thick filament assembly.

Original languageEnglish (US)
Pages (from-to)155-162
Number of pages8
JournalCell Structure and Function
Volume22
Issue number1
StatePublished - Feb 1997
Externally publishedYes

Fingerprint

Tropomyosin
Myosins
Proteins
Caenorhabditis elegans
Myosin Subfragments
Genetic Loci
Myosin Heavy Chains
Phosphoprotein Phosphatases
Mutant Proteins
Invertebrates
Post Translational Protein Processing
Genes
Vertebrates
Molecular Biology
Amino Acid Sequence
Protein Isoforms
Muscles
DNA
Population

Keywords

  • Directed assembly
  • Myosin
  • Novel thick filament proteins
  • Paramyosin

ASJC Scopus subject areas

  • Physiology
  • Structural Biology
  • Cell Biology

Cite this

Liu, F., Barral, J. M., Bauer, C. C., Ortiz, I., Cook, R. G., Schmied, M. F., & Epstein, H. F. (1997). Assemblases and coupling proteins in thick filament assembly. Cell Structure and Function, 22(1), 155-162.

Assemblases and coupling proteins in thick filament assembly. / Liu, Feizhou; Barral, Jose M.; Bauer, Christopher C.; Ortiz, Irving; Cook, Richard G.; Schmied, Michael F.; Epstein, Henry F.

In: Cell Structure and Function, Vol. 22, No. 1, 02.1997, p. 155-162.

Research output: Contribution to journalArticle

Liu, F, Barral, JM, Bauer, CC, Ortiz, I, Cook, RG, Schmied, MF & Epstein, HF 1997, 'Assemblases and coupling proteins in thick filament assembly', Cell Structure and Function, vol. 22, no. 1, pp. 155-162.
Liu F, Barral JM, Bauer CC, Ortiz I, Cook RG, Schmied MF et al. Assemblases and coupling proteins in thick filament assembly. Cell Structure and Function. 1997 Feb;22(1):155-162.
Liu, Feizhou ; Barral, Jose M. ; Bauer, Christopher C. ; Ortiz, Irving ; Cook, Richard G. ; Schmied, Michael F. ; Epstein, Henry F. / Assemblases and coupling proteins in thick filament assembly. In: Cell Structure and Function. 1997 ; Vol. 22, No. 1. pp. 155-162.
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