This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Synaptotagmin 1 mediates the Ca+2-dependent fusion of neurotransmitter-filled vesicles with the presynaptic terminus in neurons. While there is considerable structural and biochemical information on the synaptotagmin molecule, its precise function is still unclear;however, most atomic resolution structures conclude that the two tandem C2 domains of synaptotagmin were autonomous agents attached by a small linker. Due to our unique purification and crystallization method, we have captured human synaptotagmin 1 C2A-C2B in a conformation that shows contacts between domains as they exist prior to Ca+2 priming. The crystals we have analyzed at SSRL to this point reveal that areas of C2A involved in Ca+2 binding, phospholipid association and SNARE protein binding are distorted and probably inactivated through intra-molecular interactions with C2B. These interactions form a trigger mechanism designed to respond to changing Ca+2 concentrations. These conclusions will be essential to our understanding of fundamental neuronal function.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-30
Application #
7954337
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
2009-03-01
Project End
2010-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
30
Fiscal Year
2009
Total Cost
$3,515
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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