title: Effect of the viral protease on the dynamics of bacteriophage HK97 maturation intermediates characterized by variance analysis of cryo EM particle ensembles.
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.
authors.affiliation: Electrical and Computer Engineering, Cornell University, Ithaca, NY, USA. Electronic address: yg326@cornell.edu.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: dveesler@uw.edu.
authors.forename: David
authors.initials: D
authors.lastname: Veesler
authors.affiliation: Biomedical and Electrical and Computer Engineering, Cornell University, Ithaca, NY, USA. Electronic address: pd83@cornell.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doerschuk
authors.affiliation: Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: jackj@scripps.edu.
authors.forename: John E
authors.initials: JE
authors.lastname: Johnson
mesh_terms: D001435:Bacteriophages / Q000737:chemistry / Q000648:ultrastructure*; D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D008962:Models, Theoretical; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000648:ultrastructure; D019065:Virus Assembly / Q000235:genetics
chemical_list: D010447:Peptide Hydrolases
keywords: Cryo electron microscopy; Hong Kong 97 bacteriophage; Viral protease; Virus maturation