TY - JOUR
T1 - A Structure-Based Mechanism for Vesicle Capture by the Multisubunit Tethering Complex Dsl1
AU - Ren, Yi
AU - Yip, Calvin K.
AU - Tripathi, Arati
AU - Huie, David
AU - Jeffrey, Philip D.
AU - Walz, Thomas
AU - Hughson, Frederick M.
N1 - Funding Information:
We gratefully acknowledge the staff of the National Synchrotron Light Source X29 beamline for assistance with x-ray data collection; Zong Lin and Hays Rye for assistance and discussion regarding fluorescence anisotropy experiments; Hans Dieter Schmitt for sharing results prior to publication; and Sean Munro, Mary Munson, Anne Spang, and Daniel Ungar for critical comments on the manuscript. This work was supported by a grant to F.M.H. from the National Institutes of Health (GM071574). C.K.Y. acknowledges a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. T.W. is an investigator of the Howard Hughes Medical Institute.
PY - 2009/12/11
Y1 - 2009/12/11
N2 - Vesicle trafficking requires membrane fusion, mediated by SNARE proteins, and upstream events that probably include "tethering," an initial long-range attachment between a vesicle and its target organelle. Among the factors proposed to mediate tethering are a set of multisubunit tethering complexes (MTCs). The Dsl1 complex, with only three subunits, is the simplest known MTC and is essential for the retrograde traffic of COPI-coated vesicles from the Golgi to the ER. To elucidate structural principles underlying MTC function, we have determined the structure of the Dsl1 complex, revealing a tower containing at its base the binding sites for two ER SNAREs and at its tip a flexible lasso for capturing vesicles. The Dsl1 complex binds to individual SNAREs via their N-terminal regulatory domains and also to assembled SNARE complexes; moreover, it is capable of accelerating SNARE complex assembly. Our results suggest that even the simplest MTC may be capable of orchestrating vesicle capture, uncoating, and fusion.
AB - Vesicle trafficking requires membrane fusion, mediated by SNARE proteins, and upstream events that probably include "tethering," an initial long-range attachment between a vesicle and its target organelle. Among the factors proposed to mediate tethering are a set of multisubunit tethering complexes (MTCs). The Dsl1 complex, with only three subunits, is the simplest known MTC and is essential for the retrograde traffic of COPI-coated vesicles from the Golgi to the ER. To elucidate structural principles underlying MTC function, we have determined the structure of the Dsl1 complex, revealing a tower containing at its base the binding sites for two ER SNAREs and at its tip a flexible lasso for capturing vesicles. The Dsl1 complex binds to individual SNAREs via their N-terminal regulatory domains and also to assembled SNARE complexes; moreover, it is capable of accelerating SNARE complex assembly. Our results suggest that even the simplest MTC may be capable of orchestrating vesicle capture, uncoating, and fusion.
KW - CELLBIO
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U2 - 10.1016/j.cell.2009.11.002
DO - 10.1016/j.cell.2009.11.002
M3 - Article
C2 - 20005805
AN - SCOPUS:71149117138
SN - 0092-8674
VL - 139
SP - 1119
EP - 1129
JO - Cell
JF - Cell
IS - 6
ER -