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SLAC Today Article


30 January 2008

  GTPase Family Proteins Show Microscopic Teamwork

edited by Brad Plummer, SLAC Communications


Proteins are transported to specific sites within cells enclosed in packets called transport vesicles, along a specialized network of tracks called microtubules. Transport vesicles are targeted to the correct acceptor membrane by a number of sequential steps that are regulated by small GTPases of the Rab and Arf families. The initial interaction between vesicles and the target membrane is thought to be mediated by very large molecular "tethers" that link the two membranes prior to fusion. A Stanford team from the Brunger and Pfeffer laboratories has studied how one such putative tether molecule is localized to the membranes of an organelle called the Golgi complex.

The work shows that binding of the tethering protein to the Golgi requires cooperation between two families of GTPases: the Rab family and the Arl family. Only together could the two membrane-attached GTPases provide stable binding of the tether to the Golgi complex.

Using x-ray diffraction data collected at SSRL, researchers Alondra Schweizer Burguete and Timothy Fenn determined the structure of a region of the tether in complex with the Rab6 GTPase. They created a model of the system to visualize how the GTPases might cooperate to anchor the tether and thereby capture incoming vesicles. In this model, proteins belonging to the Rab and Arf GTPase families reside at the membrane-anchor point of the tether. A pair of Arl1 GTPase molecules form a previously characterized complex with the tether close to the membrane. At a significant distance (10 nanometers) away from the membrane, a pair of Rab6 molecules bind a distinct tether-region; the Rab GTPases are able to reach this far thanks to their extended and unstructured tail-domains.

The model explains how Arl1 and Rab6 GTPases may cooperate in anchoring the tether to the Golgi membrane, thereby directing incoming vesicles to the Golgi membrane prior to fusion. This represents a first-ever instance of such a cooperative relationship among different members of these GTPase families.

The results are published in the January 25 edition of the journal Cell.

Schweizer Burguete, A., Fenn T. D., Brunger, A. T. and Pfeffer, S. R. (2008). Rab and Arl GTPase Family Members Cooperate in the Localization of the Golgin GCC185. Cell 132(2), 286-298.

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