5w6l | pdb_00005w6l

Crystal Structure of RRSP, a MARTX Toxin Effector Domain from Vibrio vulnificus CMCP6

spinqualitylabelsall models 5w6l, resolution 3.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5w6l is a 2 chain structure with sequence from Vibrio vulnificus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.45Å Ligands: CL, GOL, MSE, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A3B6UEL2_VIBVL Publication Abstract from PubMed The Ras-extracellular signal-regulated kinase pathway is critical for controlling cell proliferation, and its aberrant activation drives the growth of various cancers. Because many pathogens produce toxins that inhibit Ras activity, efforts to develop effective Ras inhibitors to treat cancer could be informed by studies of Ras inhibition by pathogens. Vibrio vulnificus causes fatal infections in a manner that depends on multifunctional autoprocessing repeats-in-toxin, a toxin that releases bacterial effector domains into host cells. One such domain is the Ras/Rap1-specific endopeptidase (RRSP), which site-specifically cleaves the Switch I domain of the small GTPases Ras and Rap1. We solved the crystal structure of RRSP and found that its backbone shares a structural fold with the EreA/ChaN-like superfamily of enzymes. Unlike other proteases in this family, RRSP is not a metalloprotease. Through nuclear magnetic resonance analysis and nucleotide exchange assays, we determined that the processing of KRAS by RRSP did not release any fragments or cause KRAS to dissociate from its bound nucleotide but instead only locally affected its structure. However, this structural alteration of KRAS was sufficient to disable guanine nucleotide exchange factor-mediated nucleotide exchange and prevent KRAS from binding to RAF. Thus, RRSP is a bacterial effector that represents a previously unrecognized class of protease that disconnects Ras from its signaling network while inducing limited structural disturbance in its target. The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling.,Biancucci M, Minasov G, Banerjee A, Herrera A, Woida PJ, Kieffer MB, Bindu L, Abreu-Blanco M, Anderson WF, Gaponenko V, Stephen AG, Holderfield M, Satchell KJF Sci Signal. 2018 Oct 2;11(550). pii: 11/550/eaat8335. doi:, 10.1126/scisignal.aat8335. PMID:30279169 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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