2n9w | pdb_00002n9w
Solution NMR Structure of the membrane localization domain from the Ras/Rap1-specific endopeptidase (RRSP) of the Vibrio vulnificus multifunctional autoprocessing repeats-in-toxins (MARTX) toxin
Structural highlights
FunctionMARTX_VIBVL Precursor of a multifunctional toxin that causes destruction of the actin cytoskeleton by covalent cross-linking of actin and inactivation of Rho GTPases when translocated into the host cytoplasm. Upon translocation into the host cell, undergoes autoprocessing in cis mediated by the peptidase C80 domain (also named CPD domain): the protease activity is activated upon binding inositol hexakisphosphate (InsP6) present at the host cell membrane and delivers the Cysteine protease domain-containing toxin F3 chain to the host cytosol. The Cysteine protease domain-containing toxin F3 chain will then further cleave and release effector toxin chains that cause disassembly of the actin cytoskeleton and enhance V.vulnificus colonization of the small intestine, possibly by facilitating evasion of phagocytic cells.[UniProtKB:Q9KS12] Following autocatalytic cleavage in cis, this chain mediates processing in trans to release other individual toxin chains to the host cytosol. Released effector toxin chains cause disassembly of the actin cytoskeleton and enhance V.vulnificus colonization of the small intestine, possibly by facilitating evasion of phagocytic cells.[UniProtKB:Q9KS12] Actin-directed toxin that catalyzes the covalent cross-linking of host cytoplasmic monomeric actin. Mediates the cross-link between 'Lys-50' of one monomer and 'Glu-270' of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding. The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners. Acts as an acid--amino-acid ligase that transfers the gamma-phosphoryl group of ATP to the 'Glu-270' actin residue, resulting in the formation of an activated acyl phosphate intermediate. This intermediate is further hydrolyzed and the energy of hydrolysis is utilized for the formation of the amide bond between actin subunits.[UniProtKB:Q9KS12] N-epsilon-fatty acyltransferase that mediates lysine-palmitoylation of host Rho GTPase proteins, with a strong preference for host Rac1. After delivery to the host cytosol, localizes to the host cell membrane where it palmitoylates host Rho GTPase proteins, resulting in loss of all active GTP-bound Rho and subsequent actin depolymerization. Prenylation of host Rac1 at the C-terminus is required for lysine-palmitoylation.[UniProtKB:Q9KS12] Indirectly activates the small GTPase CDC42.[UniProtKB:Q9KS12] Publication Abstract from PubMedMembrane localization domain (MLD) was first proposed for a 4-helix-bundle motif in the crystal structure of the C1 domain of Pasteurella multocida toxin (PMT). This structure motif is also found in the crystal structures of several clostridial glycosylating toxins (TcdA, TcdB, TcsL, and TcnA). The Ras/Rap1-specific endopeptidase (RRSP) module of the multifunctional autoprocessing repeats-in-toxins (MARTX) toxin produced by Vibrio vulnificus has sequence homology to the C1-C2 domains of PMT, including a putative MLD. We have determined the solution structure for the MLDs in PMT and in RRSP using solution state NMR. We conclude that the MLDs in these two toxins assume a 4-helix-bundle structure in solution. This article is protected by copyright. All rights reserved. The membrane localization domains of two distinct bacterial toxins form a 4-helix-bundle in solution.,Hisao GS, Brothers MC, Ho M, Wilson BA, Rienstra CM Protein Sci. 2016 Dec 15. doi: 10.1002/pro.3097. PMID:27977897[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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