Single charge change on the helical surface of the paramyosin rod dramatically disrupts thick filament assembly in Caenorhabditis elegans

Keiko Gengyo-Ando, Hiroaki Kagawa

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Charge interactions between α-helical coiled-coil proteins have been postulated to determine the alignment of many filamentous proteins, such as myosin heavy-chain rod, paramyosin and α-keratin. Here we determined the sequence changes in nine mutations in the unc-15 paramyosin gene of Caenorhabditis elegans, including one nonsense, four missense, one deletion and three suppressor mutations. These mutation sites were located on a molecular model, constructed by optimizing charge interactions between paramyosin rods. Remarkably, single charge reversals (e.g., glutamic acid to lysine) were found that either disrupted or restored filament assembly in vivo. The positions of the mutations within the paramyosin molecule support the models of paramyosin assembly and further suggest that the C-terminal region containing a cluster of five mutations, and a site interacting with it, play a key role in assembly. One amino acid substitution in this C-terminal region, in which there is a "weak spot", led to a loss of reactivity with one monoclonal anti-paramyosin antibody. The results demonstrate how a single amino acid substitution can alter the assembly properties of α-helical molecules.

Original languageEnglish
Pages (from-to)429-441
Number of pages13
JournalJournal of Molecular Biology
Volume219
Issue number3
DOIs
Publication statusPublished - 1991 Jun 5
Externally publishedYes

Keywords

  • Caenorhabditis elegans
  • assembly
  • mutation
  • paramyosin
  • α-helical coiled coil

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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