A Rab Effector Called the Exocyst and Related Vesicle Tether Complexes - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 73

found to form a “Y”-shaped structure. The subunits are held together by a predicted
four-helix bundle comprised of the amino-terminal coiled-coil regions of each of
the four subunits. One leg of the “Y” formed by COG1 acts as a link to the
remaining subunits, COG 5-8 (Lees et al. 2010 ).
4.8.2 DSL1
The Dsl1 complex, required for tethering of Golgi-derived COP1 vesicles to the
ER, is the simplest of the CATCHR family, having only three subunits, Dsl1,
Sec39, and Tip20. Dsl1 and Tip20 fit the CATCHR architecture of rods formed
from stacked helical bundles (Tripathi et al. 2009 ). Sec39 is also predominantly
alpha helical, but the helices are arranged perpendicular to the long axis in a
continuous ribbon rather than in bundles. Dsl1 links Sec39 to Tip20 generating a
“Y”-shaped overall structure (Ren et al. 2009 ). The inherent flexibility of Dsl1
allows for great variability in the angle of the “Y” (Fig 4.1b ).
4.8.3 GARP
The GARP complex is required for tethering of endosome-derived vesicles to the
trans Golgi network. GARP consists of four subunits, Vps51, Vps52, Vps53, and
Vps54. Partial structures of two of them indicate structural features similar to that of
the exocyst . The carboxy terminal region of Vps53 consists of two helical bundles
in tandem (Vasan et al. 2010 ), while the carboxy terminal region of Vps54 consists
of three helical bundles (Perez-Victoria et al. 2010 ). The amino termini are
involved in assembly of the GARP complex, suggesting the possibility of higher
order parallels with the COG and Dsl1 structures.
4.9 From Structures to Functions
Understanding the functions of these four tethering complexes at a detailed mech-
anistic level has proven to be quite challenging. Many interactions with other
components of the vesicular traffic machinery have been noted and some common
themes have emerged; nonetheless, major questions still remain. What is lacking is
a coherent model describing how all of the different interactions work in concert to
direct vesicle traffic. Below some of the interactions that are common among the
different tethers are summarized together with some current ideas regarding the
roles of these interactions in the transport reactions.