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Journal of Virology, February 2009, p. 1823-1836, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01781-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nuclear Magnetic Resonance Structure Shows that the Severe Acute Respiratory Syndrome Coronavirus-Unique Domain Contains a Macrodomain Fold{triangledown}

Amarnath Chatterjee,1 Margaret A. Johnson,1 Pedro Serrano,1 Bill Pedrini,1 Jeremiah S. Joseph,3 Benjamin W. Neuman,2,6 Kumar Saikatendu,3 Michael J. Buchmeier,2 Peter Kuhn,3 and Kurt Wüthrich1,4,5*

Departments of Molecular Biology,1 Molecular and Integrative Neurosciences,2 Cell Biology,3 Chemistry,4 Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., MB-44, La Jolla, California 92037,5 School of Biological Sciences, University of Reading, Whiteknights, RG6 6AJ Reading, United Kingdom6

Received 22 August 2008/ Accepted 23 November 2008

The nuclear magnetic resonance (NMR) structure of a central segment of the previously annotated severe acute respiratory syndrome (SARS)-unique domain (SUD-M, for "middle of the SARS-unique domain") in SARS coronavirus (SARS-CoV) nonstructural protein 3 (nsp3) has been determined. SUD-M(513-651) exhibits a macrodomain fold containing the nsp3 residues 528 to 648, and there is a flexibly extended N-terminal tail with the residues 513 to 527 and a C-terminal flexible tail of residues 649 to 651. As a follow-up to this initial result, we also solved the structure of a construct representing only the globular domain of residues 527 to 651 [SUD-M(527-651)]. NMR chemical shift perturbation experiments showed that SUD-M(527-651) binds single-stranded poly(A) and identified the contact area with this RNA on the protein surface, and electrophoretic mobility shift assays then confirmed that SUD-M has higher affinity for purine bases than for pyrimidine bases. In a further search for clues to the function, we found that SUD-M(527-651) has the closest three-dimensional structure homology with another domain of nsp3, the ADP-ribose-1"-phosphatase nsp3b, although the two proteins share only 5% sequence identity in the homologous sequence regions. SUD-M(527-651) also shows three-dimensional structure homology with several helicases and nucleoside triphosphate-binding proteins, but it does not contain the motifs of catalytic residues found in these structural homologues. The combined results from NMR screening of potential substrates and the structure-based homology studies now form a basis for more focused investigations on the role of the SARS-unique domain in viral infection.

* Corresponding author. Mailing address: Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., MB-44, La Jolla, CA 92037. Phone: (858) 784-8011. Fax: (858) 784-8014. E-mail: wuthrich{at}scripps.edu

{triangledown} Published ahead of print on 3 December 2008.

Journal of Virology, February 2009, p. 1823-1836, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01781-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Serrano, P., Johnson, M. A., Chatterjee, A., Neuman, B. W., Joseph, J. S., Buchmeier, M. J., Kuhn, P., Wuthrich, K. (2009). Nuclear Magnetic Resonance Structure of the Nucleic Acid-Binding Domain of Severe Acute Respiratory Syndrome Coronavirus Nonstructural Protein 3. J. Virol. 83: 12998-13008 [Abstract] [Full Text]  


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