title: Structure of the herpesvirus major capsid protein.
abstract: Herpes simplex virus-1 (HSV-1) virions are large, complex enveloped particles containing a proteinaceous tegument layer connected to an icosahedral capsid. The major capsid protein, VP5 (149 kDa), makes up both types of capsomere, pentons and hexons. Limited trypsin digestion of VP5 identified a single stable 65 kDa fragment which represents a proposed protein folding nucleus. We report the 2.9 A crystal structure of this fragment and its modeling into an 8.5 A resolution electron cryomicroscopy map of the HSV-1 capsid. The structure, the first for any capsid protein from Herpesviridae, revealed a novel fold, placing herpesviruses outside any of the structurally linked viral groupings. Alterations in the geometrical arrangements of the VP5 subunits in the capsomeres exposes different residues, resulting in the differential association of the tegument and VP26 with the pentons and hexons, respectively. The rearrangements of VP5 subunits required to form both pentavalent and hexavalent capsomeres result in structures that exhibit very different electrostatic properties. These differences may mediate the binding and release of other structural proteins during capsid maturation.
authors.affiliation: Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Graduate Program in Structural and Computational Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Bowman
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Baker
authors.forename: Frazer J
authors.initials: FJ
authors.lastname: Rixon
authors.forename: Wah
authors.initials: W
authors.lastname: Chiu
authors.forename: Florante A
authors.initials: FA
authors.lastname: Quiocho
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D018259:Herpesvirus 1, Human / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D036022:Capsid Proteins; C442523:VP5 protein, Herpes simplex virus type 1