Structures from the SARS-CoV proteomics project
Peter Kuhn group (The Scripps Research Institute) and collaborators
Peter Kuhn's group from The Scripps Research Institute has
provided several examples of structures determined from the SARS-CoV
proteomics project using data from GM/CA-CAT (as well as from SSRL) . These
three structures include two important non-structural proteins, nsp10 and
nsp15, and the third was an RNA-binding domain of the SARS nucleocapsid. The
2.9-Å Nsp15 structure of a deletion construct truncated at both the C-
and N- terminus required extensive screening of multiple protein constructs.
This structure revealed that truncation of the N-terminal oligomerization
domains turns it from a hexameric endonuclease into an obligate monomer which
is inactive. The primary reason for the loss of catalytic activity was found
to be a dramatic collapse of the two active site loops that support the
nucleotide ligand and metal ion during catalysis.
Figure: Structure of an N-Terminal
Truncated Form of Nendou (NSP15) From SARS-CORONAVIRUS [PDB ID
Joseph, JS, Saikatendu, KS, Subramanian, V, Neuman, BW, Brooun, A, Griffith,
M, Moy, K, Yadav, MK, Velasquez, J, Buchmeier, MJ, Stevens, RC, Kuhn, P.
Crystal Structure of Nonstructural Protein 10 from the Severe Acute
Respiratory Syndrome Coronavirus Reveals a Novel Fold with Two Zinc-Binding
Motifs, J. Virol. 80 (16), 7894-7901 (2006). DOI: 10.1128/JVI.00467-06.|
Joseph, JS, Saikatendu, KS, Subramanian, V, Neuman, BW, Buchmeier, MJ,
Stevens, RC, Kuhn, P. Crystal Structure of a Monomeric Form of Severe Acute
Respiratory Syndrome Coronavirus Endonuclease nsp15 Suggests a Role for
Hexamerization as an Allosteric Switch, J. Virol. 81 (12), 6700-6708 (2007).