Identification of a tetrameric assembly domain in the C terminus of heat-activated TRPV1 channels

Feng Zhang, Shuang Liu, Fan Yang, Jie Zheng, Kewei Wang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Transient receptor potential (TRP) channels as cellular sensors are thought to function as tetramers. Yet, the molecular determinants governing channel multimerization remain largely elusive. Here we report the identification of a segment comprising21amino acids(residues752-772 of mouse TRPV1) after the known TRP-like domaininthe channel Cterminus that functions as a tetrameric assembly domain (TAD). Purified recombinant C-terminal proteins of TRPV1-4, but not the N terminus, mediated the protein-protein interaction in an in vitro pulldown assay. Western blot analysis combined with electrophysiology and calcium imaging demonstrated that TAD exerted a robust dominant-negative effect on wild-type TRPV1. When fused with the membrane-tethered peptide Gap43, the TAD blocked the formation of stable homomultimers. Calcium imaging and current recordings showed that deletion of the TAD in a poreless TRPV1 mutant subunit suppressed its dominant-negative phenotype, confirming the involvement of the TAD in assembly of functional channels. Our findings suggest that the C-terminal TAD in TRPV1 channels functions as a domain that is conserved among TRPV1-4 and mediates a direct subunit-subunit interaction for tetrameric assembly.

Original languageEnglish (US)
Pages (from-to)15308-15316
Number of pages9
JournalJournal of Biological Chemistry
Issue number17
StatePublished - Apr 29 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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