Revised Crystal Structure of Human Adenovirus Reveals the Limits on Protein IX Quasi-Equivalence and on Analyzing Large Macromolecular Complexes

S. Kundhavai Natchiar, Sangita Venkataraman, Tina Marie Mullen, Glen R. Nemerow, Vijay S. Reddy

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

We report the revised crystal structure of a pseudo-typed human adenovirus at 3.8-Å resolution that is consistent with the atomic models of minor proteins determined by cryo-electron microscopy. The diffraction data from multiple crystals were rescaled and merged to increase the data completeness. The densities for the minor proteins were initially identified in the phase-refined omit maps that were further improved by the phases from docked poly-alanine models to build atomic structures. While the trimeric fiber molecules are disordered due to flexibility and imposition of 5-fold symmetry, the remaining major capsid proteins hexon and penton base are clearly ordered, with the exception of hypervariable region 1 of hexons, the RGD containing loop, and the N-termini of the penton base. The exterior minor protein IX together with the interior minor proteins IIIa and VIII stabilizes the adenovirus virion. A segment of N-terminal pro-peptide of VI is found in the interior cavities of peripentonal hexons, and the rest of VI is disordered. While the triskelion substructures formed by the N-termini of IX conform to excellent quasi 3-fold symmetry, the tetrameric coiled-coils formed by the C-termini and organized in parallel and anti-parallel arrangement do not exhibit any quasi-symmetry. This observation also conveys the pitfalls of using the quasi-equivalence as validation criteria for the structural analysis of extended (non-modular) capsid proteins such as IX. Together, these results remedy certain discrepancies in the previous X-ray model in agreement with the cryo-electron microscopy models.

Original languageEnglish (US)
Pages (from-to)4132-4141
Number of pages10
JournalJournal of Molecular Biology
Volume430
Issue number21
DOIs
StatePublished - Oct 19 2018
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge the support from National Institutes of Health grants AI070771 and AI103692 to V.S.R. and HL054352 to G.R.N. We thank Nhung Huynh for her assistance with data collection. We also thank Dr. Bob Fischetti and coworkers at GM/CA beamline at the Advance Photon Source, Chicago, for technical support with the synchrotron data collection. G.M./C.A. has been funded with federal funds from the National Institutes of Health (Y1-CO-1020, Y1-GM-11040), and the Advance Photon Source is supported by US Department of Energy under the contract DE-AC02-06CH11357. The authors would like to thank Dr. Tom Goddard for his expert advice on using special features of the Chimera program.

Funding Information:
We acknowledge the support from National Institutes of Health grants AI070771 and AI103692 to V.S.R. and HL054352 to G.R.N. We thank Nhung Huynh for her assistance with data collection. We also thank Dr. Bob Fischetti and coworkers at GM/CA beamline at the Advance Photon Source, Chicago, for technical support with the synchrotron data collection. G.M./C.A. has been funded with federal funds from the National Institutes of Health ( Y1-CO-1020 , Y1-GM-11040 ), and the Advance Photon Source is supported by US Department of Energy under the contract DE-AC02-06CH11357. The authors would like to thank Dr. Tom Goddard for his expert advice on using special features of the Chimera program.

Publisher Copyright:
© 2018 Elsevier Ltd

Keywords

  • adenovirus
  • crystal structure
  • minor proteins
  • protein IX
  • quasi-equivalence

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