Snijder, H.J. et al. Structural evidence for dimerization-regulated activation of an integral membrane phospholipase. Nature 401, 717-721

Laboratory of Biophysical Chemistry, BIOSON Research Institute, University of Groningen, The Netherlands.
Nature (Impact Factor: 41.46). 11/1999; 401(6754):717-21. DOI: 10.1038/44890
Source: PubMed


Dimerization is a biological regulatory mechanism employed by both soluble and membrane proteins. However, there are few structural data on the factors that govern dimerization of membrane proteins. Outer membrane phospholipase A (OMPLA) is an integral membrane enzyme which participates in secretion of colicins in Escherichia coli. In Campilobacter and Helicobacter pylori strains, OMPLA is implied in virulence. Its activity is regulated by reversible dimerization. Here we report X-ray structures of monomeric and dimeric OMPLA from E. coli. Dimer interactions occur almost exclusively in the apolar membrane-embedded parts, with two hydrogen bonds within the hydrophobic membrane area being key interactions. Dimerization results in functional oxyanion holes and substrate-binding pockets, which are absent in monomeric OMPLA. These results provide a detailed view of activation by dimerization of a membrane protein.

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    • "The association of two enzymes interacting via the flat barrel side creates a dimeric complex with two extended clefts along the subunit interface that bind the substrate [57]. The architecture of the substrate binding clefts and the catalytic site allows productive binding of substrates with either one or two acyl chains of various lengths [57]. The enteric pathogen Yersinia pseudotuberculosis, which causes human gastroenteritis and mesenteric lymphadenitis, encodes an outer membrane PLase A 2 named PldA, which is active against PC and SM [58]. "
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    • "The fact that the truncated OmpA-1-276 and OmpA-188-276 were also able to form dimers suggests that in the context of the dimer, the soluble domains are not integrating into this proposed 16-stranded pore. Dimerization as a mechanism to regulate an enzymatic role is also plausible, as seen for the dimeric OmpA (OmpLA) (Snijder et al., 1999). OmpA by contrast has no known enzymatic activity. "
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