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26
CATCHR-Family Tethering Complexes: Structure and
Mechanism
Frederick Hughson 1 , Yi Ren 1 , Joshua Lees 1 , Philip Jeffrey 1 , Calvin Yip 2 , Thomas Walz 2, 3 .
Department of Molecular Biology, Princeton University, Princeton, NJ 08544 1 , Department of
Cell Biology, Harvard Medical School, Boston, MA 02115 2 , Howard Hughes Medical Institute,
Harvard Medical School, Boston, MA 02115 3
Abstract:
We seek to understand the protein machinery that guides the movement and fusion of
intracellular transport vesicles. Several of our current projects entail structural and mechanistic
studies of large multi-subunit tethering complexes of the CATCHR (Complex Associated with
Tethering Containing Helical Rods) family. CATCHR-family tethering factors (COG, Dsl1,
exocyst, and GARP) function in the capture of cargo-laden vesicles and may orchestrate the
activities of other components of the trafficking machinery, including SNAREs and coat
proteins. We are investigating the structure and function of these complexes using x-ray
crystallography, electron microscopy, site-directed mutagenesis, in vitro reconstitution, and a
suite of spectroscopic techniques. Our results for the COG and Dsl1 complexes help elucidate
their architecture and flexibility, their interaction with SNARE and coat proteins, and the
mechanisms through which they regulate SNARE complex assembly and membrane fusion.