3WRX: Crystal structure of helicase complex 1

Citation:
Abstract
The tomato mosaic virus (ToMV) resistance gene Tm-1 encodes a protein that shows no sequence homology to functionally characterized proteins. Tm-1 binds ToMV replication proteins and thereby inhibits replication complex formation. ToMV mutants that overcome this resistance have amino acid substitutions in the helicase domain of the replication proteins (ToMV-Hel). A small region of Tm-1 in the genome of the wild tomato Solanum habrochaites has been under positive selection during its antagonistic coevolution with ToMV. Here we report crystal structures for the N-terminal inhibitory domains of Tm-1 and a natural Tm-1 variant with an I91-to-T substitution that has a greater ability to inhibit ToMV RNA replication and their complexes with ToMV-Hel. Each complex contains a Tm-1 dimer and two ToMV-Hel monomers with the interfaces between Tm-1 and ToMV-Hel bridged by ATP. Residues in ToMV-Hel and Tm-1 involved in antagonistic coevolution are found at the interface. The structural differences between ToMV-Hel in its free form and in complex with Tm-1 suggest that Tm-1 affects nucleoside triphosphatase activity of ToMV-Hel, and this effect was confirmed experimentally. Molecular dynamics simulations of complexes formed by Tm-1 with ToMV-Hel variants showed how the amino acid changes in ToMV-Hel impair the interaction with Tm-1 to overcome the resistance. With these findings, together with the biochemical properties of the interactions between ToMV-Hel and Tm-1 variants and effects of the mutations in the polymorphic residues of Tm-1, an atomic view of a step-by-step coevolutionary arms race between a plant resistance protein and a viral protein emerges.
PDB ID: 3WRXDownload
MMDB ID: 122279
PDB Deposition Date: 2014/2/27
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.5  Å
Source Organism:
Tobacco mosaic virus strain tomato/L
Similar Structures:
Biological Unit for 3WRX: dimeric; determined by author and by software (PISA)
Molecular Components in 3WRX
Label Count Molecule
Proteins (2 molecules)
1
Tm-1 Protein
Molecule annotation
1
Replicase Large Subunit(Gene symbol: ToMVgp2)
Molecule annotation
Chemicals (12 molecules)
1
2
2
2
3
8
* Click molecule labels to explore molecular sequence information.

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