Long-Range Communication between Different Functional Sites in the Picornaviral 3C Protein

Yan M. Chan, Ibrahim M. Moustafa, Jamie J. Arnold, Craig E. Cameron, David D. Boehr

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Summary The 3C protein is a master regulator of the picornaviral infection cycle, responsible for both cleaving viral and host proteins, and interacting with genomic RNA replication elements. Here we use nuclear magnetic resonance spectroscopy and molecular dynamics simulations to show that 3C is conformationally dynamic across multiple timescales. Binding of peptide and RNA lead to structural dynamics changes at both the protease active site and the RNA-binding site, consistent with these sites being dynamically coupled. Indeed, binding of RNA influences protease activity, and likewise, interactions at the active site affect RNA binding. We propose that RNA and peptide binding re-shapes the conformational energy landscape of 3C to regulate subsequent functions, including formation of complexes with other viral proteins. The observed channeling of the 3C energy landscape may be important for regulation of the viral infection cycle.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalStructure
Volume24
Issue number4
DOIs
StatePublished - Apr 5 2016

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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