Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector

Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.

Formation and Turnover of NSF- and SNAP-containing “Fusion” Complexes Occur on Undocked, Clathrin-coated Vesicle–derived Membranes

Specificity of vesicular transport is determined by pair-wise interaction between receptors (SNAP receptors or SNAREs) associated with a transport vesicle and its target membrane. Two additional factors, N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (SNAP) are ubiquitous components of vesicular transport pathways. However, the precise role they play is not known. On the basis that NSF and SNAP can be recruited to preformed SNARE complexes, it has been proposed that NSF- and SNAP-containing complexes are formed after SNARE-dependent docking of transport vesicles. This would enable ATPase-dependent complex disassembly to be coupled directly to membrane fusion. Alternatively, binding and release of NSF/SNAP may occur before vesicle docking, and perhaps be involved in the activation of SNAREs. To gain more information about the point at which so-called 20S complexes form during the transport vesicle cycle, we have examined NSF/SNAP/SNARE complex turnover on clathrin-coated vesicle–derived membranes in situ. This has been achieved under conditions in which the extent of membrane docking can be precisely monitored. We demonstrate by UV-dependent cross-linking experiments, coupled to laser light-scattering analysis of membranes, that complexes containing NSF, SNAP, and SNAREs will form and dissociate on the surface of undocked transport vesicles.

DOE/EPA/NSF/ONR joint program on bioremediation : interagency announcement of opportunity : Environmental Protection Agency, Department of Energy, National Science Foundation, Office of Naval Research jointly announce the availability of 1996 grants for research.

Mode of access: Internet.

University funding: information on the role of peer review at NSF and NIH.

Mode of access: Internet.

The NSF science development programs.

Mode of access: Internet.

A report on a special NSF summer, 1964, computer program for undergraduates /

Mode of access: Internet.

Fuel gas production from solid waste : final report (covering the period June 28, 1973 to December 31, 1974) NSF Contract C-827 ... /

"PB-245 083."

A study of NSF teacher enhancement program (TEP) participants and principal investigators, 1984-1989 /

"NSF 94-58"--Vol. 2, cover p. [4].

Teacher preparation awards : NSF collaboratives for excellence in teacher preparation awards : fiscal year 1996.

"NSF 96-146 (replaces NSF 96-82)"--P. [4] of cover.

Research study of criteria and procedures for evaluating scientific information retrieval systems; final report. Prepared for Office of Science Information Service, National Science Foundation, Washington, D.C., contract NSF-C218.

"AD 273 115."

Catalogue of IGY all-sky camera data for United States stations. IGY project no. 45.3. NSF grant no. Y/45.3/240.

Mode of access: Internet.

Abstracts of NSF/RANN research reports : private sector productivity /

Mode of access: Internet.