| Structural highlights
6siu is a 4 chain structure with sequence from Hiss2 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | ibpA, p76, HSM_1489 (HISS2), CDC42 (HUMAN) |
| Activity: | Small monomeric GTPase, with EC number 3.6.5.2 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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] [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
Various pathogenic bacteria use post-translational modifications to manipulate the central components of host cell functions. Many of the enzymes released by these bacteria belong to the large Fic family, which modify targets with nucleotide monophosphates. The lack of a generic method for identifying the cellular targets of Fic family enzymes hinders investigation of their role and the effect of the post-translational modification. Here, we establish an approach that uses reactive co-substrate-linked enzymes for proteome profiling. We combine synthetic thiol-reactive nucleotide derivatives with recombinantly produced Fic enzymes containing strategically placed cysteines in their active sites to yield reactive binary probes for covalent substrate capture. The binary complexes capture their targets from cell lysates and permit subsequent identification. Furthermore, we determined the structures of low-affinity ternary enzyme-nucleotide-substrate complexes by applying a covalent-linking strategy. This approach thus allows target identification of the Fic enzymes from both bacteria and eukarya.
Identification of targets of AMPylating Fic enzymes by co-substrate-mediated covalent capture.,Gulen B, Rosselin M, Fauser J, Albers MF, Pett C, Krisp C, Pogenberg V, Schluter H, Hedberg C, Itzen A Nat Chem. 2020 Aug;12(8):732-739. doi: 10.1038/s41557-020-0484-6. Epub 2020 Jul, 6. PMID:32632184[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ 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
- ↑ Gulen B, Rosselin M, Fauser J, Albers MF, Pett C, Krisp C, Pogenberg V, Schluter H, Hedberg C, Itzen A. Identification of targets of AMPylating Fic enzymes by co-substrate-mediated covalent capture. Nat Chem. 2020 Aug;12(8):732-739. doi: 10.1038/s41557-020-0484-6. Epub 2020 Jul, 6. PMID:32632184 doi:http://dx.doi.org/10.1038/s41557-020-0484-6
|
