- SB, Massachusetts Institute of Technology
- PhD, Yale University
- Assistant Professor, Molecular Physiology and Biological Physics
- Phone: 434-243-1413
- Email: email@example.com
Biochemical, biophysical, structural, and cell biological studies of intracellular membrane tethering and fusion
Our lab uses biochemical, biophysical, structural, and cell biological techniques to study the molecular mechanisms underlying intracellular membrane tethering and fusion in eukaryotes.
Research in the lab centers around a six-subunit complex called HOPS (homotypic vacuole fusion and protein sorting). HOPS is needed for fusion of yeast vacuoles (analogous to lysosomes in metazoan cells) and for traffic from the Golgi apparatus and endosomes to the vacuole.
HOPS is an effector for the vacuolar Rab GTPase Ypt7p, that is, it is recruited to membranes by GTP-bound Ypt7p. It also interacts with vacuolar “SNARE” proteins. (SNAREs are thought to directly catalyze membrane fusion through formation of membrane-bridging “trans-SNARE complexes”.) Clearly, HOPS is a central regulator of membrane tethering and fusion, but the biochemical mechanisms by which it functions are still unknown.
Our lab has three main areas of interest:
1. Biochemical and biophysical studies of reconstituted membrane tethering and fusion reactions:
a. What intermolecular interactions mediate membrane tethering?
b. How does the HOPS complex regulate SNARE complex assembly?
c. How does the HOPS complex regulate the activity of SNARE complexes for membrane fusion?
2. Structural studies of HOPS and its interactions with Rab GTPases, SNAREs, and membranes, using X-ray crystallography and scattering techniques, as well as single-particle cryo-electron microscopy.
3. Cell biological investigation of how the HOPS complex mediates autophagy (a stress-response pathway that is, among other things, protective towards ischemic cell damage following heart attack and stroke).
- The yeast vacuolar Rab GTPase Ypt7p has an activity beyond membrane recruitment of the homotypic fusion and protein sorting-Class C Vps complex. The Biochemical journal. 2012;443(1): 205-11. PMID: 22417749
- Autophagy: cells SNARE selves. Current biology : CB. 2011;21(18): R697-9. PMID: 21959158
- Hickey C, Stroupe C, Wickner W. The major role of the Rab Ypt7p in vacuole fusion is supporting HOPS membrane association. The Journal of biological chemistry. 2009;284(24): 16118-25. PMID: 19386605 | PMCID: PMC2713515
- Stroupe C, Hickey C, Mima J, Burfeind A, Wickner W. Minimal membrane docking requirements revealed by reconstitution of Rab GTPase-dependent membrane fusion from purified components. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(42): 17626-33. PMID: 19826089 | PMCID: PMC2764952
- Stroupe C, Collins K, Fratti R, Wickner W. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. The EMBO journal. 2006;25(8): 1579-89. PMID: 16601699 | PMCID: PMC1440844
- Ota N, Stroupe C, Ferreira-da-Silva J, Shah S, Mares-Guia M, Brunger A. Non-Boltzmann thermodynamic integration (NBTI) for macromolecular systems: relative free energy of binding of trypsin to benzamidine and benzylamine. Proteins. 2000;37(4): 641-53. PMID: 10651279
- Stroupe C, Brunger A. Crystal structures of a Rab protein in its inactive and active conformations. Journal of molecular biology. 2000;304(4): 585-98. PMID: 11099382