title: In the virion, the 11-amino-acid peptide cofactor pVIc is covalently linked to the adenovirus proteinase.
abstract: Previously, the adenovirus proteinase (AVP) had been shown to be stimulated by an 11-amino-acid cofactor pVIc; the crystal structure of an AVP-pVIc complex formed in vitro reveals a disulfide bond between AVP and pVIc. However, that disulfide bond was recently shown not to be required for maximal stimulation of enzyme activity by pVIc in vitro. Is the disulfide bond physiologically relevant or is it an artifact that arose in the crystallization of the complex? Here we show that a disulfide bond between AVP and pVIc is physiologically relevant, because in the virus particle AVP is linked to pVIc via a disulfide bond. This is also the first experimental proof that AVP interacts in vivo with one of its cofactors, all of which were discovered and characterized in vitro. A rationale as to why this apparently unnecessary disulfide bond between AVP and pVIc forms in the virus particle is presented.
authors.affiliation: Biology Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: McGrath
authors.forename: Katharine S
authors.initials: KS
authors.lastname: Aherne
authors.forename: Walter F
authors.initials: WF
authors.lastname: Mangel
mesh_terms: D000260:Adenoviruses, Human / Q000378:metabolism*; D000596:Amino Acids; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004220:Disulfides; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D014771:Virion / Q000378:metabolism
chemical_list: D000596:Amino Acids; D036022:Capsid Proteins; D004220:Disulfides; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D014764:Viral Proteins; C105093:glycyl-valyl-glutaminyl-seryl-leucyl-lysyl-arginyl-arginyl-arginyl-cysteinyl-phenylalanine; C090876:polypeptide VI, adenovirus; D003546:Cysteine Endopeptidases; C091827:adenain