Modeling Suggests TRPC3 Hydrogen Bonding and Not Phosphorylation Contributes to the Ataxia Phenotype of the Moonwalker Mouse

A gain-of-function mutation (T635A) in the transient receptor potential (TRP) channel TRPC3 results in abnormal channel gating and causes cerebellar ataxia in the dominant Moonwalker (Mwk) mouse mutant. However, the underlying molecular and structural mechanisms are unclear. Here, we used a combined approach of computational modeling and functional characterization of proposed TRPC3 mutants. Our findings support a mechanism by which the hydrogen bonding capability of threonine 635 plays a significant role in maintaining a stable, closed state channel. This capability is lost in the Mwk mutant, suggesting a structural basis for the disease-causing phenotype in the Mwk mouse.

• Publication year

  2015

• Venue

  Biochemistry

• Publication date

  2015-06-26

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/acs.biochem.5b00235PMID 26112884PMCID 4530436
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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