PLoS ONE (Jan 2014)

Solution structure of the 2A protease from a common cold agent, human rhinovirus C2, strain W12.

  • Woonghee Lee,
  • Kelly E Watters,
  • Andrew T Troupis,
  • Nichole M Reinen,
  • Fabian P Suchy,
  • Kylie L Moyer,
  • Ronnie O Frederick,
  • Marco Tonelli,
  • David J Aceti,
  • Ann C Palmenberg,
  • John L Markley

DOI
https://doi.org/10.1371/journal.pone.0097198
Journal volume & issue
Vol. 9, no. 6
p. e97198

Abstract

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Human rhinovirus strains differ greatly in their virulence, and this has been correlated with the differing substrate specificity of the respective 2A protease (2Apro). Rhinoviruses use their 2Apro to cleave a spectrum of cellular proteins important to virus replication and anti-host activities. These enzymes share a chymotrypsin-like fold stabilized by a tetra-coordinated zinc ion. The catalytic triad consists of conserved Cys (C105), His (H34), and Asp (D18) residues. We used a semi-automated NMR protocol developed at NMRFAM to determine the solution structure of 2Apro (C105A variant) from an isolate of the clinically important rhinovirus C species (RV-C). The backbone of C2 2Apro superimposed closely (1.41-1.81 Å rmsd) with those of orthologs from RV-A2, coxsackie B4 (CB4), and enterovirus 71 (EV71) having sequence identities between 40% and 60%. Comparison of the structures suggest that the differential functional properties of C2 2Apro stem from its unique surface charge, high proportion of surface aromatics, and sequence surrounding the di-tyrosine flap.