Membrane fusion protein

Currently, five different molecular classes of mdr efflux pumps are known [5], While pumps of the the ATP-binding cassette (ABC) transporter superfamily are driven by ATP hydrolysis, the other four superfamilies called resistance-nodulation-division (RND), major facilitator superfamily (MFS), multidrug and toxic compound extrusion (MATE), and small multidrag resistance transporter (SMR) are driven by the proton-motive force across the cytoplasmic membrane. Usually a single pump protein is located within the cytoplasmic membrane. However, the RND-type pumps which are restricted to Gram-negative bacteria consist of two additional components, a periplasmic membrane fusion protein (MFP) which connects the efflux pump to an outer... 

KieUan M, Rey FA (2006) Virus membrane-fusion proteins more than one way to make a hairpin. Nat Rev Microbiol 4 67-76... 

White, ]., Kielian, M. and Helnius, A. (1983) Membrane fusion proteins of enveloped animal viruses. 

The RND family of efflux pumps are restricted to gram-negative organisms and consists of three major components the RND pump, a periplasmic membrane fusion protein (MFP), and an outer-membrane factor (OMF). Together these three proteins are able to effectively pump a variety of antibiotics, dyes, and ions depending on the type of RND pump associated with the system (Figure 3.2). The... 

Figure 3.2. A representative RND efflux pump system. This system is comprised of three essential components The RND pump (e.g., AcrD and MexX) is located on the cytoplasmic membrane and is responsible for the recognition of substrates in the cytosol, including aminoglycosides, and moving them into the periplasmic space. The membrane fusion protein (MFP) (e.g., AcrA and MexY) is responsible for moving the substrate across the periplasm the final component is the outer membrane factor (OMF) (e.g., TolC and OprM) that provides a conduit for the substrate to the extracellular region of the cell.

Singh, M., Berger, B., and Kim, P. S. (1999). LearnCoil-VMF Computational evidence for coiled-coil-like motifs in many viral membrane-fusion proteins./. Mol. Biol. 290, 1031-1041. 

White, J.M. (1990) Viral and cellular membrane fusion proteins. Annu. Rev. Physiol., 52, 675-697. 

Kelly RB, von Wedel RJ, Strong PN (1979) Phospholipase-dependent and phospholipase-independent inhibition of transmitter relase by beta-bungarotoxin. Adv Cytopharmacol 3 77-85 Kerner (1817) Vergiftung durch verborbene Wurste. Tubinger Blatter 3 1-25 Kielian M, Rey FA (2006) Virus membrane-fusion proteins more than one way to make a hairpin. Nat Rev Microbiol 4 67-76... 

These structural studies on the alphavirus and flavivirus membrane fusion proteins strengthen the relationship between these virus families, but apparently distance them from the trimeric influenza and retrovirus envelope assemblies. However, low pH specifically triggers not only a conformational change in alphavirus and flavivirus surface proteins, but also an oligomerization switch to a trimeric state (Allison et ah, 1995). This... 

Members of several RND, MFS, and ABC snbfamilies have been proposed to function in combination with a periplasmic membrane fusion protein (MFP) and an onter membrane protein (OMP) to generate a single energy-conpled tripartite efflnx system across both membranes of the gram-negative bacteria. The best characterized tripartite systems are MexAB-OprM from Pseudomonas aeruginosa and, by far, AcrAB-TolC from Escherichia coli. 

Akama, H., Matsuura, T., Kashiwagi, S., Yoneyama, H.. Narita, S., Tsukihara, T., Nakagawa, A., and Nakae, T. (2004) Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. The Journal of Biological Chemistry,... 

A.R. (2003) Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA. The Journal of Bioiogicai Chemistry, 278 (15), 12903-12912. 

Krishnamoorthy, G., Tikhonova, E.B., and Zgurskaya, H.I. (2008) Fitting periplasmic membrane fusion proteins to inner membrane transporters mutations that enable Escherichia coli AcrA to fimction with Pseudomonas aeruginosa MexB. Journal of Bacteriology. 190 (2), 691-698. 

Tikhonova, E.B., Devroy, V.K., lan S.Y., and Zgurskaya, H.I. (2007) Reconstitution of the Escherichia coli macrolide transporter the periplasmic membrane fusion protein MacA stimulates the ATPase activity of MacB. Molecular Microbiology, 63 (3), 895-910. 

One criterion for a bona fide membrane-fusion protein is that membrane fusion can be reconstituted by transfection of the candidate fusion protein into nonfusing cells or by reconstitution into lipid vesicles (White, 1990 White, 1992 White and Blobel, 1989). Transfection of meltrin a into fibroblasts did not lead to an increase in cell fusion (Yagami-Hiromasa et al., 1995). Clearly, failure to reconstitute fusion does not rule out a role in fusion because the cellular fusion machinery may be more complex than viral fusion proteins. Muscle cells might contain other proteins that are required for meltrin a to promote membrane fusion but that are not expressed or active in fibroblasts. Ultimately, the identity of a bona fide cell-cell fusion protein or protein machine will only be determined by reconstituting membrane fusion with defined components. In the interim, it will be important to more accurately understand the roles of meltrin a and fertilin in the cascade of steps that result in membrane fusion and thereby perhaps distinguish between a direct and indirect role in fusion. 

Earp LJ, Delos SE, Park HE, White JM (2005) The many mechanisms of viral membrane fusion proteins. Curr Top Microbiol Immunol 285 25-66... 

Transporters, which mediate multidrug efflux, have usually been divided into four classes depending on (1) whether they are conducted by proton motive force (PMF) or by ATP, and (2) whether they consist of a single protein that has any one of the 4-, 12-, or 14-transmembrane-spanning domains [194,195] or whether they are a more complex multicomponent transporter [183]. The more complex transporters, in addition to a multidrug efflux protein (MexB, for example), contain a membrane fusion protein sueh as MexA and an outer membrane protein such as OprM [194]. 

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