Effectors of Rab GTPases: Rab Binding Specificity and Their Role in Coordination of Rab Function and Localization - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 44

Fig. 3.2 Structural features of Rab proteins and their conformational changes upon nucleotide
exchange. The comparison of the GTP and the GDP-bound structure of Sec4p is shown (PDB ID
1G16/1G17, Stroupe and Brunger ( 2000 )). In the GTP-bound structure switch I is colored in red ,
switch II is colored in green , the p-loop is blue , the interswitch regions are yellow, and the CDRs
(complementary determining regions) are shown in pink (numbered 1-3 from N to C-terminus).
The bound GTP is depicted in dark gray . Aromatic residues forming the Rab hydrophobic triad are
shown in sticks and labeled with one letter amino acid code. The largest conformational changes
occur within the switch regions

cell biology experiments is challenging, as off-target effects could lead to results
that are difficult to interpret. Generally, mutations in the CDRs might have the
highest potential to only influence Rab:effector interactions as these regions are not
significantly involved in the interaction with other proteins and also seem to be
partially responsible for effector specificity.

3.2.3 Rab:Effector Binding Sites

The large amount of available structures of Rab proteins in complex with effectors
makes it possible to compare the interaction sites of different effector proteins. In
Fig. 3.4 , Rab:effector structures are depicted in which the interacting residues are
represented by spheres. The structures have been sorted according to the size of the
interacting surface area on the Rab proteins (as listed in Table 3.2 ). The surface area
on the Rab protein that is buried upon effector complex formation ranges from
560

2 . The smallest interaction area is observed in the Rab5:EAA1
complex, which also represents the smallest RBD structure solved to date. However
for the other effectors, the buried area is not correlated to the size of the RBD.
To evaluate the conservation of the residues involved in Rab:effector interac-
tions, we have performed a sequence alignment of all Rab proteins that are present

2

Å to 1860 Å