Bcl-2


The Bcl-2 family of proteins regulate programmed cell death (apoptosis) by an unknown mechanism. This process is a strictly regulated device for removing unnecessary, aged or damaged cells. Abnormal resistance to apoptosis causes malformations, autoimmune disease or cancer. In contrast, enhanced apoptotic decay of cells may play a role in both acute diseases and chronic pathologies. Naturally, there is a great interest in atomic structure of these proteins. A structure of human inhibitor of apoptosis, Bcl-XL, has been determined by both X-ray and NMR. No coordinates for a long flexible loop (residues 28-80) were determined, since no electron density and insufficient NOEs were observed for this fragment. Mutation studies suggest, however, that serine phosphorylation in the flexible loop region of Bcl-2 has a very important regulatory function. The program FANTOM is being used to model the structure of the flexible loop.


References:

  1. Korsmeyer, S.J. (1995) Trends Genet. 11, 101.
  2. Kroemer, G. (1997) Nature Med. 3, 614.
  3. Muchmore, S.W.; Sattler, M.; Liang, H.; Meadows, R.P.; Harlan, J.E.; Yoon, H.S.; Nwettesheim, D.; Chang, B.S.; Thompson, C.B.; Wong, S.L.; Ng, S.C.; Fesik, S.W. (1996) Nature 381, 335.
  4. Ito, T.; Deng, X.; Carr, B.; May, W.S. (1997) J. Biol. Chem. 272, 11671.

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