| Structural highlights
4itr is a 4 chain structure with sequence from Haemophilus somnus 2336 and Homo sapiens. This structure supersedes the now removed PDB entry 3n3v. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | ibpA, p76, HSM_1489 (Haemophilus somnus 2336), CDC42 (Homo sapiens) |
| Activity: | Nicotinamide-nucleotide adenylyltransferase, with EC number 2.7.7.1 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[IBPA_HAES2] 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] [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.[5] [6] [7]
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[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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
- ↑ 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
- ↑ Gauthier-Campbell C, Bredt DS, Murphy TH, El-Husseini Ael-D. Regulation of dendritic branching and filopodia formation in hippocampal neurons by specific acylated protein motifs. Mol Biol Cell. 2004 May;15(5):2205-17. Epub 2004 Feb 20. PMID:14978216 doi:10.1091/mbc.E03-07-0493
- ↑ Oceguera-Yanez F, Kimura K, Yasuda S, Higashida C, Kitamura T, Hiraoka Y, Haraguchi T, Narumiya S. Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. J Cell Biol. 2005 Jan 17;168(2):221-32. Epub 2005 Jan 10. PMID:15642749 doi:10.1083/jcb.200408085
- ↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200
- ↑ 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
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