3wrw
From Proteopedia
Crystal structure of the N-terminal domain of resistance protein
Structural highlights
FunctionTM1R_SOLLC Inhibitor of viral RNA replication which confers resistance to some tobamoviruses including tomato mosaic virus (ToMV) (e.g. isolate L), tobacco mosaic virus (TMV), tobacco mild green mosaic virus (TMGMV) and pepper mild mottle virus (PMMoV), but not to resistance-breaking isolates of ToMV (e.g. LT1, SL-1 and ToMV1-2) and tomato brown rugose fruit virus (ToBRFV) (PubMed:17238011, PubMed:17699618, PubMed:19423673, PubMed:23415925, PubMed:28107419, PubMed:29582165, PubMed:3686829). Prevents tobamoviruses RNA replication by affecting the association of tobamoviruses replication proteins (large and small subunits) with host membrane-associated proteins (e.g. TOM1, TOM2A and ARL8), thus inhibiting the replication complex formation on the membranes and avoiding viral negative-strand RNA synthesis (PubMed:17699618, PubMed:19423673, PubMed:23415925, PubMed:23658455). Inhibits triphosphatase activity of ToMV replication proteins (PubMed:25092327).[1] [2] [3] [4] [5] [6] [7] [8] [9] Publication Abstract from PubMedThe 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. Structural basis for the recognition-evasion arms race between Tomato mosaic virus and the resistance gene Tm-1.,Ishibashi K, Kezuka Y, Kobayashi C, Kato M, Inoue T, Nonaka T, Ishikawa M, Matsumura H, Katoh E Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):E3486-95. doi:, 10.1073/pnas.1407888111. Epub 2014 Aug 4. PMID:25092327[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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