The synthesis and hydrolysis of ATP by the F1F0 ATP synthase are of central importance to all of biochemistry: the complex is the primary producer of biology's energetic currency. However, the details of how proton translocation couples with ATP synthesis are not well understood, because a high-resolution structure of the membrane-bound portion of the complex is not available. This assembled F0 portion, like many membrane protein complexes, has thus far resisted study by diffraction methods and solution NMR due to its heterogeneity and large effective molecular weight. Studies of ATP synthase (especially subunit c)--by incorporation of 13C, 15N, 19F, and 2H isotopic labels and solid state nuclear magnetic resonance (SSNMR) distance, torsion angle and relaxation measurements-will determine F0 structure and dynamics. In particular, the conformational changes that take place in subunit c upon uptake and release of protons at the essential aspartic acid residue will be carefully explored. These experiments will enhance the understanding of the molecular details of ion conduction, and the methodology developed and refined in the process will be directly applicable to many membrane proteins, responsible for energy transduction, cellular recognition, and many regulatory processes. The structural data and methods derived from this work, therefore, will be of utility for revealing the molecular mechanisms underlying membrane-related diseases such as cancer and AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020134-03
Application #
6385085
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Cassatt, James
Project Start
1999-09-17
Project End
Budget Start
2001-09-17
Budget End
2002-06-20
Support Year
3
Fiscal Year
2001
Total Cost
$31,788
Indirect Cost
Name
Columbia University (N.Y.)
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027