Effect of the viral protease on the dynamics of bacteriophage HK97 maturation intermediates characterized by variance analysis of cryo EM particle ensembles

Yunye Gong; David Veesler; Peter C Doerschuk; John E Johnson

doi:10.1016/j.jsb.2015.12.012

Effect of the viral protease on the dynamics of bacteriophage HK97 maturation intermediates characterized by variance analysis of cryo EM particle ensembles

J Struct Biol. 2016 Mar;193(3):188-195. doi: 10.1016/j.jsb.2015.12.012. Epub 2015 Dec 24.

Authors

Yunye Gong¹, David Veesler², Peter C Doerschuk³, John E Johnson⁴

Affiliations

¹ Electrical and Computer Engineering, Cornell University, Ithaca, NY, USA. Electronic address: [email protected].
² Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: [email protected].
³ Biomedical and Electrical and Computer Engineering, Cornell University, Ithaca, NY, USA. Electronic address: [email protected].
⁴ Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: [email protected].

PMID: 26724602
DOI: 10.1016/j.jsb.2015.12.012

Abstract

Cryo EM structures of maturation-intermediate Prohead I of bacteriophage HK97 with (PhI(Pro+)) and without (PhI(Pro-)) the viral protease packaged have been reported (Veesler et al., 2014). In spite of PhI(Pro+) containing an additional ∼ 100 × 24 kD of protein, the two structures appeared identical although the two particles have substantially different biochemical properties, e.g., PhI(Pro-) is less stable to disassembly conditions such as urea. Here the same cryo EM images are used to characterize the spatial heterogeneity of the particles at 17Å resolution by variance analysis and show that PhI(Pro-) has roughly twice the standard deviation of PhI(Pro+). Furthermore, the greatest differences in standard deviation are present in the region where the δ-domain, not seen in X-ray crystallographic structures or fully seen in cryo EM, is expected to be located. Thus presence of the protease appears to stabilize the δ-domain which the protease will eventually digest.

Keywords: Cryo electron microscopy; Hong Kong 97 bacteriophage; Viral protease; Virus maturation.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Bacteriophages / chemistry
Bacteriophages / ultrastructure*
Capsid / chemistry
Capsid / ultrastructure*
Cryoelectron Microscopy*
Crystallography, X-Ray
Models, Theoretical
Peptide Hydrolases / chemistry*
Peptide Hydrolases / ultrastructure
Virus Assembly / genetics

Substances

Peptide Hydrolases