4aui

Publication Abstract from PubMed

The outer membrane of Gram-negative bacteria contains a large number of channel forming proteins, porins, for the uptake of small nutrient molecules. N. gonorrhoeae porins of the serotype A (PorBIA) are associated with disseminating diseases and mediate a rapid bacterial invasion into host cells in a phosphate-sensitive manner. To gain insights into this structure-function relationship we analyzed PorBIA by X-ray crystallography in the presence of phosphate and ATP. The structure of PorBIA in the complex solved at a resolution of 3.3 A displays a surplus of positive charges inside the channel. ATP ligand binding in the channel is coordinated by positively charged residues of the channel interior. These residues are ligating the aromatic, sugar and pyrophosphate moieties of the ligand. Two phosphate ions were observed in the structure, one of which clamped by two arginine residues (R92 and R124) localized at the extraplasmic channel exit. A short b-bulge in the b2-strand together with the long L3 loop narrow the barrel diameter significantly and further support substrate specificity through H-bond interactions. Interestingly, the structure also comprised a small peptide as remnant of a periplasmic protein which physically links porin molecules to the peptidoglycan network. To test the importance of R92 on bacterial invasion the residue was mutated. In vivo assays of bacteria carrying the R92S mutation confirmed the importance of this residue for host cell invasion. Furthermore, systematic sequence and structure comparisons of PorBIA from Neisseriaceae indicated the R92 residue to be unique in disseminating N. gonorrhoeae thereby possibly distinguishing invasion-promoting porins from other neisserial porins.

Structure and function of the PorB porin from disseminating N. gonorrhoeae.,Zeth K, Kozjak-Pavlovic V, Faulstich M, Fraunholz M, Hurwitz R, Kepp O, Rudel T Biochem J. 2012 Oct 25. PMID:23095086^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.