Speaker: Dr. Paul Horton, Computational Biology Research Center, Advanced Industrial Science and Technology (AIST), Tokyo, Japan
Time: 1:00-2:00pm, Tuesday, March 17th, 2009
Place: 321 Stanley Hall
Abstract:
In this talk I will introduce recent experimental and bioinformatics results
which have changed our view of the mitochondrial outer membrane proteome.
Mitochondria are believed to have evolved from ancestors of the alphaproteobacteria, which have outer membranes populated by numerous proteins, exclusively of beta-barrel architecture, representing 2-3% of their proteomes. In the light of this fact and some preliminary analysis, mitochondria were expected to have perhaps 100 Mitochondrial β-barrel Outer Membrane Proteins (MBOMPs) (Wimley 2003). In contrast to that expectation, and despite the availability of whole genome sequences for several eukaryotes, only 5 types of MBOMPs have been identified (Tom40, Porin, Mdm10, Sam50 and Mmm2). Moreover, the sequence characteristics responsible for localization and membrane integration of these proteins was unknown.
Recently a breakthrough was reported by (Kutik et al., 2008), who discovered a C-terminal region signal sequence Po.G..Hy.Hy, (Po = polar, Hy = large hydrophobic residue) which they named the β-signal. They showed experimentally that 3 of the 5 known MBOMPs possess and require this signal, and argued from evolutionary conservation that a 4th MBOMP also possesses a functional β-signal. Our group considered the newly discovered β-signal as an opportunity to search the genome for the “missing” MBOMP's expected to be lurking in the proteome. To our surprise, instead of finding multiple new candidates (we did identify one candidate which is currently being tested by a collaborator), we instead found indirect but convincing evidence that the estimated number of MBOMP's should probably be reduced by an order of magnitude. In my talk I will discuss the results of our informatics analysis of the mitochondrial proteome in light of the β-signal and the recently announced NMR structure of human VDAC-1 (Hiller et al. 2008).
References:
Imai, K., Gromiha, M. and Horton, P. (2008). Cell 135(7), 1158-9. Abstract, PDF,
Kutik, S., Stojanovski, D., Becker, L., Becker, T., Meinecke, M., Krueger, V, Prinz, C., Guiard, B., Wanger, R., Pfanner, N., and Weidermann N. (2008). Cell 132, 1011-1024. Abstract.
Neupert, W., and Hermann, J. (2007), Annu. Rev. Biochem. 76, 723-749. Abstract.
Hiller, S., Garces, R., Malia, T., Orekhov, V., Colombini, M., and Wagner, G. (2008). Science 321, 1206-1210. Abstract.
White, S. (2008). Membrane Proteins of Known 3D Structure.
Wimley, W. (2003), Curr. Opin. Struct. Biol., 13, 404-411. Abstract.
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