Arati Tripathi

Publications (2)45.11 Total impact

• Article: A structure-based mechanism for vesicle capture by the multisubunit tethering complex Dsl1.

  Yi Ren, Calvin K Yip, Arati Tripathi, David Huie, Philip D Jeffrey, Thomas Walz, Frederick M Hughson
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  ABSTRACT: 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.
  Cell 12/2009; 139(6):1119-29. · 32.40 Impact Factor
• Article: Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex.

  Arati Tripathi, Yi Ren, Philip D Jeffrey, Frederick M Hughson
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  ABSTRACT: Multisubunit tethering complexes are essential for intracellular trafficking and have been proposed to mediate the initial interaction between vesicles and the membranes with which they fuse. Here we report initial structural characterization of the Dsl1p complex, whose three subunits are essential for trafficking from the Golgi apparatus to the endoplasmic reticulum (ER). Crystal structures reveal that two of the three subunits, Tip20p and Dsl1p, resemble known subunits of the exocyst complex, establishing a structural connection among several multisubunit tethering complexes and implying that many of their subunits are derived from a common progenitor. We show, moreover, that Tip20p and Dsl1p interact directly via N-terminal alpha-helices. Finally, we establish that different Dsl1p complex subunits bind independently to different ER SNARE proteins. Our results map out two alternative protein-interaction networks capable of tethering COPI-coated vesicles, via the Dsl1p complex, to ER membranes.
  Nature Structural &#38 Molecular Biology 02/2009; 16(2):114-23. · 12.71 Impact Factor