3cjb

<StructureSection load='3cjb' size='340' side='right' caption='[[3cjb]], [[Resolution|resolution]] 3.21&Aring;' scene=''>

<table><tr><td colspan='2'>[[3cjb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CJB FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cjc|3cjc]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3cjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cjb OCA], [http://pdbe.org/3cjb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cjb RCSB], [http://www.ebi.ac.uk/pdbsum/3cjb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cjb ProSAT]</span></td></tr>

== Disease ==

[[http://www.uniprot.org/uniprot/GELS_HUMAN GELS_HUMAN]] Defects in GSN are the cause of amyloidosis type 5 (AMYL5) [MIM:[http://omim.org/entry/105120 105120]]; also known as familial amyloidosis Finnish type. AMYL5 is a hereditary generalized amyloidosis due to gelsolin amyloid deposition. It is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure.<ref>PMID:2157434</ref> <ref>PMID:2153578</ref> <ref>PMID:2176481</ref> <ref>PMID:1338910</ref>

[[http://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT]] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [[http://www.uniprot.org/uniprot/GELS_HUMAN GELS_HUMAN]] Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis.<ref>PMID:20393563</ref>

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cj/3cjb_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

The Gram-negative bacterium Vibrio cholerae is the causative agent of a severe diarrheal disease that afflicts three to five million persons annually, causing up to 200,000 deaths. Nearly all V. cholerae strains produce a large multifunctional-autoprocessing RTX toxin (MARTX(Vc)), which contributes significantly to the pathogenesis of cholera in model systems. The actin cross-linking domain (ACD) of MARTX(Vc) directly catalyzes a covalent cross-linking of monomeric G-actin into oligomeric chains and causes cell rounding, but the nature of the cross-linked bond and the mechanism of the actin cytoskeleton disruption remained elusive. To elucidate the mechanism of ACD action and effect on actin, we identified the covalent cross-link bond between actin protomers using limited proteolysis, X-ray crystallography, and mass spectrometry. We report here that ACD catalyzes the formation of an intermolecular iso-peptide bond between residues E270 and K50 located in the hydrophobic and the DNaseI-binding loops of actin, respectively. Mutagenesis studies confirm that no other residues on actin can be cross-linked by ACD both in vitro and in vivo. This cross-linking locks actin protomers into an orientation different from that of F-actin, resulting in strong inhibition of actin polymerization. This report describes a microbial toxin mechanism acting via iso-peptide bond cross-linking between host proteins and is, to the best of our knowledge, the only known example of a peptide linkage between nonterminal glutamate and lysine side chains.

 

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== References ==

[[Category: Human]]

[[Category: Kudryashov, D S]]

[[Category: Pashkov, I]]

[[Category: Reisler, E]]

[[Category: Sawaya, M R]]

[[Category: Yeates, T O]]

[[Category: Structural protein]]