Structural Basis for Bc12-Regulated Mitochondrion-Dependent Apoptosis

Abstract

The Bcl-2 family proteins are key regulators of programmed cell death, in health and major human diseases, including cancer. Their pro- or anti-apoptotic functions are regulated by subcellular location, as the proteins cycle between soluble and membrane-bound forms; by dimerization with other Bcl-2 family members; by binding to other non-homologous proteins; and by formation of membrane pores that are believed to regulate apoptosis by perturbing mitochondrial physiology. The solution structures of several Bcl-2 family proteins are very similar despite their antagonistic activities, however, the structures of the membrane-associated proteins are not known and may be key to their opposing functions. The goals of this project are: (I) to determine the structures of the membrane-associated Bcl-2 proteins; and (2) to determine their mechanism of apoptosis regulation. The research strategy combines NMR structure determination in lipid environments with biological assays carried out in parallel with structure determination.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2005
Accession Number
ADA437659

Entities

People

  • Francesca M. Marassi

Organizations

  • Sanford Burnham Prebys Medical Discovery Institute

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Anti-Bacterial Agents
  • Biochemistry
  • Biomedical And Dental Materials
  • Breast Cancer
  • Cells
  • Cellular Structures
  • Chemical Synthesis
  • Chemistry
  • Magnetic Resonance
  • Medical Personnel
  • Membrane Lipids
  • Nuclear Magnetic Resonance
  • Polymer Chemistry
  • Polymeric Films
  • Proteins
  • Spectroscopy

Fields of Study

  • Chemistry

Readers

  • Molecular Biology and Genetics
  • Oncology (Cancer Research).