2bov | pdb_00002bov
Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase
Structural highlights
Function[RALA_HUMAN] Multifunctional GTPase involved in a variety of cellular processes including gene expression, cell migration, cell proliferation, oncogenic transformation and membrane trafficking. Accomplishes its multiple functions by interacting with distinct downstream effectors. Acts as a GTP sensor for GTP-dependent exocytosis of dense core vesicles. Plays a role in the early stages of cytokinesis and is required to tether the exocyst to the cytokinetic furrow. The RALA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling. Key regulator of LPAR1 signaling and competes with ADRBK1 for binding to LPAR1 thus affecting the signaling properties of the receptor. Required for anchorage-independent proliferation of transformed cells.[1] [2] [3] [ARC3_CBDP] ADP-ribosylates eukaryotic Rho and Rac proteins on an asparagine residue. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedC3 exoenzymes (members of the ADP-ribosyltranferase family) are produced by Clostridium botulinum (C3bot1 and -2), Clostridium limosum (C3lim), Bacillus cereus (C3cer), and Staphylococcus aureus (C3stau1-3). These exoenzymes lack a translocation domain but are known to specifically inactivate Rho GTPases in host target cells. Here, we report the crystal structure of C3bot1 in complex with RalA (a GTPase of the Ras subfamily) and GDP at a resolution of 2.66 A. RalA is not ADP-ribosylated by C3 exoenzymes but inhibits ADP-ribosylation of RhoA by C3bot1, C3lim, and C3cer to different extents. The structure provides an insight into the molecular interactions between C3bot1 and RalA involving the catalytic ADP-ribosylating turn-turn (ARTT) loop from C3bot1 and helix alpha4 and strand beta6 (which are not part of the GDP-binding pocket) from RalA. The structure also suggests a molecular explanation for the different levels of C3-exoenzyme inhibition by RalA and why RhoA does not bind C3bot1 in this manner. Molecular recognition of an ADP-ribosylating Clostridium botulinum C3 exoenzyme by RalA GTPase.,Holbourn KP, Sutton JM, Evans HR, Shone CC, Acharya KR Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5357-62. Epub 2005 Apr 4. PMID:15809419[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
