Two structurally homologous GTPase domains interact directly during
signal recognition particle (SRP) mediated co-translational targeting of
proteins to the membrane. The
2.05Å structure of a complex of the 'NG' GTPase domains of Ffh and FtsY reveals
a remarkably symmetric heterodimer sequestering a composite active site that
contains two bound nucleotides.
The structure explains the coordinate activation of the two
GTPases. Conformational changes
coupled to formation of their extensive interface may function allosterically
to signal formation of the targeting complex to the signal-sequence binding
site and the translocon. We
propose that the complex represents a molecular 'latch', and that its
disengagement is regulated by completion of assembly of the GTPase active site.
PDB id: 1OKK
Comment
This structure is remarkable - a 'scarily-symmetric homo-heterodimer' (as it's still refered to in our PDB entry). The two SRP GTPases assemble in a GTP-dependent interaction that buries the nucleotides within a composite active site. The coordinate rearrangement of the 'latch' interface (illustrated at right) plays a key role in assembly of the symmetric interface. The 'Supporting Online Material' for this paper is important to the story - read it!
A News & Views in Nature Structural & Molecular Biology commented on this work: Mandon EC & Gilmore R (2004) 'GTPase twins in the SRP family', Nat Struct & Mol Biol., 11 115-116. It may also be interesting to read this paper alongside that from the UCSF group published simultaneously: Egea, PF, Shan, S, Napetschnig, J., Savage, DF, Walter, P, Stroud, RM (2004) 'Substrate twinning activates the signal recognition particle and its receptor' Nature 427, 215-221