Pasteurella multocida Toxin Activates Various Heterotrimeric G Proteins by Deamidation 英文参考文献.docVIP

Toxins 2010, 2, 205-214; doi:10.3390/toxins2020205 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Pasteurella multocida Toxin Activates Various Heterotrimeric G Proteins by Deamidation Joachim H. C. Orth and Klaus Aktories * Institute for Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104 Freiburg, Germany; E-Mail: Joachim.Orth@pharmakol.uni-freiburg.de * Author to whom correspondence should be addressed; E-Mail: Klaus.Aktories@pharmakol.uni-freiburg.de; Tel.: +49-761-203-5301; Fax: +49-761-203-5311. Received: 24 November 2009; in revised form: 19 January 2010 / Accepted: 27 January 2010 / Published: 28 January 2010 Abstract: Pasteurella multocida produces a 146-kDa protein toxin (Pasteurella multocida toxin, PMT), which stimulates diverse cellular signal transduction pathways by activating heterotrimeric G proteins. PMT deamidates a conserved glutamine residue of the α-subunit of heterotrimeric G proteins that is essential for GTP-hydrolysis, thereby arresting the G protein in the active state. The toxin substrates are Gαq Gα13 and the Gαi-family proteins. Activation of these α-subunits causes stimulation of phospholipase Cβ, Rho-guanine nucleotide exchange factors or inhibition of adenylyl cyclase. This article provides the current knowledge on PMT concerning the structure-function analysis based on the crystal structure and recently elucidated molecular mode of action. Furthermore, the impact of PMT on cellular signaling is discussed. Keywords: G protein; α-subunit; deamidation; GTPase; Gαq; Gαi; Gα12/13 1. Introduction Pasteurella multocida is a Gram negative opportunistic pathogenic bacterium living in the nasal, pharyngeal space of animals. Human infections occur usually by scratches and bites of domesticated animals (e.g., mainly cats and dogs). In addition, contact with salvia is sufficient for colonization of bacteria [1]. P. multocida is of particular