|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of IbpAFic2-H3717A in complex with adenylylated Cdc42== | | ==Crystal Structure of IbpAFic2-H3717A in complex with adenylylated Cdc42== |
| - | <StructureSection load='4itr' size='340' side='right' caption='[[4itr]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4itr' size='340' side='right'caption='[[4itr]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4itr]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiss2 Hiss2] and [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3n3v 3n3v]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ITR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ITR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4itr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Histophilus_somni_2336 Histophilus somni 2336] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3n3v 3n3v]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ITR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ITR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ibpA, p76, HSM_1489 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=228400 HISS2]), CDC42 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4itr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4itr OCA], [https://pdbe.org/4itr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4itr RCSB], [https://www.ebi.ac.uk/pdbsum/4itr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4itr ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nicotinamide-nucleotide_adenylyltransferase Nicotinamide-nucleotide adenylyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.1 2.7.7.1] </span></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=4itr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4itr OCA], [http://pdbe.org/4itr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4itr RCSB], [http://www.ebi.ac.uk/pdbsum/4itr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4itr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IBPA_HISS2 IBPA_HISS2]] Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.<ref>PMID:12631474</ref> <ref>PMID:19362538</ref> <ref>PMID:20622875</ref> <ref>PMID:9317034</ref> [[http://www.uniprot.org/uniprot/CDC42_HUMAN CDC42_HUMAN]] Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.<ref>PMID:14978216</ref> <ref>PMID:15642749</ref> <ref>PMID:17038317</ref> | + | [https://www.uniprot.org/uniprot/IBPA_HISS2 IBPA_HISS2] Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.<ref>PMID:12631474</ref> <ref>PMID:19362538</ref> <ref>PMID:20622875</ref> <ref>PMID:9317034</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
Line 20: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[GTP-binding protein|GTP-binding protein]] | + | *[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hiss2]] | + | [[Category: Histophilus somni 2336]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Nicotinamide-nucleotide adenylyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dixon, J E]] | + | [[Category: Dixon JE]] |
| - | [[Category: Xiao, J]] | + | [[Category: Xiao J]] |
| - | [[Category: Adenosine monophosphate-protein transferase]]
| + | |
| - | [[Category: Fic domain]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
IBPA_HISS2 Adenylyltransferase involved in virulence by mediating the addition of adenosine 5'-monophosphate (AMP) to specific tyrosine residue of host Rho GTPases RhoA, Rac and Cdc42. The resulting AMPylation inactivates Rho GTPases, thereby inhibiting actin assembly in infected cells. Probably also acts as a cysteine protease, which may play a central role after invasion of host cell and in virulence. Possible member (with IbpB) of a 2 partner secretion. Probably able to bind bovine epithelial cells (host cells). May participate in the formation of fibrils at the surface of the bacteria.[1] [2] [3] [4]
Publication Abstract from PubMed
The Fic family of adenylyltransferases, defined by a core HPFx(D/E)GN(G/K)R motif, consists of over 2,700 proteins found in organisms from bacteria to humans. The immunoglobulin-binding protein A (IbpA) from the bacterial pathogen Histophilus somni contains two Fic domains that adenylylate the switch1 tyrosine residue of Rho-family GTPases, allowing the bacteria to subvert host defenses. Here we present the structure of the second Fic domain of IbpA (IbpAFic2) in complex with its substrate, Cdc42. IbpAFic2-bound Cdc42 mimics the GDI-bound state of Rho GTPases, with both its switch1 and switch2 regions gripped by IbpAFic2. Mutations disrupting the IbpAFic2-Cdc42 interface impair adenylylation and cytotoxicity. Notably, the switch1 tyrosine of Cdc42 is adenylylated in the structure, providing the first structural view for this post-translational modification. We also show that the nucleotide-binding mechanism is conserved among Fic proteins and propose a catalytic mechanism for this recently discovered family of enzymes.
Structural basis of Fic-mediated adenylylation.,Xiao J, Worby CA, Mattoo S, Sankaran B, Dixon JE Nat Struct Mol Biol. 2010 Aug;17(8):1004-10. Epub 2010 Jul 11. PMID:20622875[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sanders JD, Bastida-Corcuera FD, Arnold KF, Wunderlich AC, Corbeil LB. Genetic manipulation of immunoglobulin binding proteins of Haemophilus somnus. Microb Pathog. 2003 Mar;34(3):131-9. PMID:12631474
- ↑ Worby CA, Mattoo S, Kruger RP, Corbeil LB, Koller A, Mendez JC, Zekarias B, Lazar C, Dixon JE. The fic domain: regulation of cell signaling by adenylylation. Mol Cell. 2009 Apr 10;34(1):93-103. doi: 10.1016/j.molcel.2009.03.008. PMID:19362538 doi:http://dx.doi.org/10.1016/j.molcel.2009.03.008
- ↑ Xiao J, Worby CA, Mattoo S, Sankaran B, Dixon JE. Structural basis of Fic-mediated adenylylation. Nat Struct Mol Biol. 2010 Aug;17(8):1004-10. Epub 2010 Jul 11. PMID:20622875 doi:10.1038/nsmb.1867
- ↑ Corbeil LB, Bastida-Corcuera FD, Beveridge TJ. Haemophilus somnus immunoglobulin binding proteins and surface fibrils. Infect Immun. 1997 Oct;65(10):4250-7. PMID:9317034
- ↑ Xiao J, Worby CA, Mattoo S, Sankaran B, Dixon JE. Structural basis of Fic-mediated adenylylation. Nat Struct Mol Biol. 2010 Aug;17(8):1004-10. Epub 2010 Jul 11. PMID:20622875 doi:10.1038/nsmb.1867
|
