Volume 15 Issue 7, July 2008

Every field of research has influential papers that have shaped and guided future work. Reinhard Jahn gives his picks for membrane fusion and a little bit of history about how the field has developed.

The cooperative action of multiple trans SNARE complexes are a likely requirement for successful membrane fusion. New in vitro analyses reveal the kinetic timescales of the sequential steps of the fusion process, beginning with trans SNARE pairing and clustering of vesicle SNARE proteins, proceeding to hemifusion of outer bilayer leaflets, and ending with full fusion.

Complexin is one of several regulatory molecules known to be important for SNARE-mediated fusion that occurs during neurotransmitter release. In vitro data now suggest that complexin plays inhibitory and Ca²⁺- dependent stimulatory roles that may be correlated to changing interactions with the SNARE complex.

Both genomic and antigenomic hepatitis delta virus (HDV) RNAs have hairpin-shaped ends. Small capped RNAs have now been identified from both genomic and antigenomic RNAs, and the human homolog of the Arabidopsis RNA amplification factor (SDE3) has been implicated in the replication of HDV.

The origin of replication located at the human DBF4 promoter is finely characterized. Two initiation zones are on opposite strands and 400 bp apart, being fired in a sequential way, in a manner similar to replication at bacterial oriC.

Polysulfides are chains of sulfur atoms abundant in extreme environments. Some organisms reduce polysulfides, and this reaction may be coupled to respiratory processes. Now the structure of the multicomponent membrane complex that catalyzes this reaction is solved, revealing a potential proton channel that could have a role in energy conservation.

Rtt109 is a relatively recently identified yeast histone acetyltransferase that forms distinct complexes with two histone chaperones. The structure of Rtt109 now reveals that while functionally distinct, it is structurally homologous to mammalian p300/CBP, which previously appeared to not contain a counterpart in yeast.

Group II chaperonins, such as TriC/CCT, have a build-in lid that can cover the folding chamber and functions in an analogous way to the GroES-like proteins used by their Group I counterparts. Structural and modeling data suggest an allosteric mechanism of TriC lid closure that differs from GroES–GroEL systems.

The protective antigen (PA) moiety of anthrax toxin exists as a stable prepore, converting into the pore form under low pH to translocate the enzymatic components across the host cell membrane. The PA pore rapidly aggregates in solution, and it is now shown that the chaperone GroEL can stabilize the PA pore, allowing single-particle EM analysis. This method could be useful for other membrane protein complexes.

Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) molecules produced by many viruses and activates an inflammatory response. Synthetic dsRNAs such as small interfering RNAs have been shown to activate TLR3. Now the TLR3 ectodomain is found to contain two dsRNA binding sites, and the implications for dsRNA recognition and selectivity and downstream signaling are discussed.

Cytoplasmic O-GlcNac modification of proteins is thought to have dynamic interplay with phosphorylation and thus be involved in regulation of signaling processes. The complete structure of an OGT homolog is now presented, suggesting how diverse ligands can be presented to the active site of the enzyme.

The fusion of biological membranes is a controlled process that occurs when two closely apposed membrane compartments are brought together so that their contents can be mixed. Membrane fusion is critical for communication between membrane-bound compartments in eukaryotic cells and is essential for host cell infection by enveloped viruses. This special focus on membrane fusion, comprised of an Essay and five Reviews, describes fundamental fusion processes and the interactions that regulate them.