Revised Crystal Structure of Human Adenovirus Reveals the Limits on Protein IX Quasi-Equivalence and on Analyzing Large Macromolecular Complexes |
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Authors: | S. Kundhavai Natchiar Sangita Venkataraman Tina-Marie Mullen Glen R. Nemerow Vijay S. Reddy |
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Affiliation: | 1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA;2. Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA |
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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. |
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Keywords: | adenovirus crystal structure minor proteins quasi-equivalence protein IX HAdVs Human adenoviruses AdVs adenoviruses cryo-EM cryo-electron microscopy PPH peripentonal hexon PB penton base NT N-terminal CT C-terminal AVP adenoviral protease NTD NT domain MDLD middle domain CTD CT domain 4-HLXB four-helical coiled-coil pVIn N-terminal pro-peptide of VI |
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