Rlf is a guanine nucleotide exchange factor for the small G-proteins RalA and
RalB and couples Ras- to Ral-signalling. Here the crystal structure of the
catalytic module of Rlf consisting of a REM- and a CDC25-homology domain is
determined. The structure is distinguished by an extended three stranded
β-sheet called the flagpole. The flagpole is a conserved element in the RalGDS
family of guanine nucleotide exchange factors and stabilises the orientation of
the REM-domain relative to the CDC25-homology domain. A proline-rich sequence in
the flagpole is unique to Rlf and several proteins that interact with this
sequence by SH3 domains are identified. Conformational pre-selection results in
a gain of affinity and contributes to the establishment of SH3 domain
selectivity.
