title: On the catalytic mechanism of bacteriophage HK97 capsid crosslinking.
abstract: During maturation of the phage HK97 capsid, each of the 415 capsid subunits forms covalent bonds to neighboring subunits, stabilizing the capsid. Crosslinking is catalyzed not by a separate enzyme but by subunits of the assembled capsid in response to conformational rearrangements during maturation. This report investigates the catalytic mechanism. Earlier work established that the crosslinks are isopeptide (amide) bonds between side chains of a lysine on one subunit and an asparagine on another subunit, aided by a catalytic glutamate on a third subunit. The mature capsid structure suggests that the reaction may be facilitated by the arrival of a valine with the lysine to complete a hydrophobic pocket surrounding the glutamate, lysine and asparagine. We show that this valine has an essential role for efficient crosslinking, and that any of six other amino acids can successfully substitute for valine. Evidently none of the remaining 13 amino acids will work.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: DanJu
authors.initials: D
authors.lastname: Tso
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Peebles
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Maurer
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Duda
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA. Electronic address: rhx@pitt.edu.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Hendrix
mesh_terms: D001435:Bacteriophages / Q000737:chemistry* / Q000502:physiology; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins
keywords: Bacteriophage assembly; Capsid stabilization; Covalent cross-linking; Genetic selection; Virus capsids; Virus maturation