Phylogenetic profiles reveal structural/functional determinants of TRPC3 signal-sensing antennae

Kyung Dae Ko, Gaurav Bhardwaj, Yoojin Hong, Gue Su Chang, Kirill Kiselyov, Damian B. van Rossum, Randen L. Patterson

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Biochemical assessment of channel structure/function is incredibly challenging. Developing computational tools that provide these data would enable translational research, accelerating mechanistic experimentation for the bench scientist studying ion channels. Starting with the premise that protein sequence encodes information about structure, function and evolution (SF&E), we developed a unified framework for inferring SF&E from sequence information using a knowledge-based approach. The Gestalt Domain Detection Algorithm-Basic Local Alignment Tool (GDDA-BLAST) provides phylogenetic profiles that can model, ab initio, SF&E relationships of biological sequences at the whole protein, single domain and single-amino acid level.1,2 In our recent paper,4 we have applied GDDA-BLAST analysis to study canonical TRP (TRPC) channels1 and empirically validated predicted lipid-binding and trafficking activities contained within the TRPC3 TRP_2 domain of unknown function. Overall, our in silico, in vitro, and in vivo experiments support a model in which TRPC3 has signal-sensing antennae which are adorned with lipid-binding, trafficking and calmodulin regulatory domains. In this Addendum, we correlate our functional domain analysis with the cryo-EM structure of TRPC3.3 In addition, we synthesize recent studies with our new findings to provide a refined model on the mechanism(s) of TRPC3 activation/deactivation.

Original languageEnglish (US)
Pages (from-to)133-137
Number of pages5
JournalCommunicative and Integrative Biology
Volume2
Issue number2
StatePublished - Mar 2009
Externally publishedYes

Keywords

  • Diacylglycerol
  • GDDA-BLAST
  • Lipid
  • Phylogenetic profile
  • SNARE
  • Transient receptor potential channel
  • TRP_2 domain

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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    Ko, K. D., Bhardwaj, G., Hong, Y., Chang, G. S., Kiselyov, K., van Rossum, D. B., & Patterson, R. L. (2009). Phylogenetic profiles reveal structural/functional determinants of TRPC3 signal-sensing antennae. Communicative and Integrative Biology, 2(2), 133-137.