Allosteric signaling and a nuclear exit strategy: binding of UL25/UL17 heterodimers to DNA-Filled HSV-1 capsids

Mol Cell. 2007 May 25;26(4):479-89. doi: 10.1016/j.molcel.2007.04.010.

Abstract

UL25 and UL17 are two essential minor capsid proteins of HSV-1, implicated in DNA packaging and capsid maturation. We used cryo-electron microscopy to examine their binding to capsids, whose architecture observes T = 16 icosahedral geometry. C-capsids (mature DNA-filled capsids) have an elongated two-domain molecule present at a unique, vertex-adjacent site that is not seen at other quasiequivalent sites or on unfilled capsids. Using SDS-PAGE and mass spectrometry to analyze wild-type capsids, UL25 null capsids, and denaturant-extracted capsids, we conclude that (1) the C-capsid-specific component is a heterodimer of UL25 and UL17, and (2) capsids have additional populations of UL25 and UL17 that are invisible in reconstructions because of sparsity and/or disorder. We infer that binding of the ordered population reflects structural changes induced on the outer surface as pressure builds up inside the capsid during DNA packaging. Its binding may signal that the C-capsid is ready to exit the nucleus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Allosteric Regulation
  • Capsid / metabolism*
  • Capsid / ultrastructure*
  • Capsid Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • Cryoelectron Microscopy
  • Dimerization
  • Herpesvirus 1, Human / metabolism*
  • Herpesvirus 1, Human / ultrastructure*
  • Image Processing, Computer-Assisted
  • Mass Spectrometry
  • Protein Binding
  • Protein Transport
  • Viral Proteins / metabolism

Substances

  • Capsid Proteins
  • Viral Proteins
  • DNA cleavage and packaging proteins, Herpesvirus