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 48

Table 3.2 Comparison of Rab:effector interaction surfaces and affinities

Buried
area b /

#ofH
bonds b

# of salt
bridges b

2

Rab Effector PDB ID Å K d /nM

Rab5a EEA1 3MJH 560 7 0 2,400

Rab22 Rabenosyn-5 (HR2) 1Z0J 670.5 10 3 9,700

Rab6a GCC185 3BBP 675.1 9 4 2,300

Rab5a Rabaptin-5 1TU3 727.8 8 1

Rab6a R6IP1 3CWZ 749.4 9 10

250/(40) a

Rab11a FIP2 4C4P 774.5 5 7

Rab25 FIP2 3TSO 840.4 8 3 650

Rab4a Rabenosyn-5

(Heptad repeats)

1Z0K 893.8 14 6 6,200

Rab11a FIP3 2HV8 944.1 13 6 290

Rab8a OCRL(539-901) 3QBT 954.9 16 7 900

Rab11a MyoVb 4LX0 979.6 7 0 254

(13.4) a Rab27a Slp2-a 3BC1 985.2 9 6

Rab7a RILP 1YHN 1,265.6 13 10
Rab3a Rabphilin-3a 1ZBD 1,426.5 9 6
Rab27(a)/b Slac2-a/melanophilin 2ZET 1,860.2 21 9 (112) a
a Brackets mark affinities that were not described in the same publication; for the Rab27:Slac2-a
interaction, the affinity was determined for Rab27a while the structure of Rab27b and Slac2-a was
determined.
b Calculated using PISA v1.48 ( http://www.ebi.ac.uk/msd-srv/prot_int/cgi-bin/piserver ) (Krissinel
and Henrick 2007 ).

their effectors using the most conserved parts of the protein—switch I, switch II,
and the interswitch region. The largest interaction areas are observed in the
complexes where the interaction between Rab and effector protein is extended
towards the less conserved CDRs. The effector binding specificity is defined by the
Rab amino acid composition of the binding site. The strictly conserved residues
within the Rab effector binding sites contribute to Rab-family specific effector
recognition. Each RBD binds to its specific subset of Rab proteins. This subset
recognition is achieved by residues that are only conserved within the subset of Rab
proteins that are recognized by a specific effector (Eathiraj et al. 2005 ).
Non-conserved residues within the interaction site support the recognition of
individual Rabs. Rab4 and Rab5 for example selectively bind to the two distinct

Fig. 3.4 (continued) depicted as spheres . The switch regions are colored in red (switch I) and
green (switch II), and the interswitch regions are shown in yellow . Interacting residues on Rab
proteins are colored according to their conservation determined by sequence alignment of all Rab
proteins in published Rab:effector structures [performed with The ConSurf Server (Glaser
et al. 2003 ; Landau et al. 2005 )]. Interacting residues of the effector proteins are colored according
to the properties of the amino acid (hydrophobic, charged, neutral). The structures were sorted
according to the size of the interacting area on the Rab protein as summarized in Table 3.2