The Signal Recognition Particle (SRP) co-translational protein targeting pathway is conserved through evolution and plays a fundamental role in the biology of cells. SRP binds to the translating ribosome, recognizing the signal peptide of the emerging polypeptide and targeting it to a membrane-associated receptor. The SRP is a ribonucleoprotein which, in prokaryotes, comprises the 4.5S RNA and the protein Ffh. Its receptor, in prokaryotes a protein called FtsY, is a structural homolog of Ffh. Both Ffh and FtsY are GTPases - they interact directly to assemble the SRP targeting complex at the membrane.
Our
laboratory is studying the structural basis for regulation of the assembly and
disengagement of these two GTPases, Ffh and FtsY. The SRP GTPases are structurally similar to other well-known
members of the GTPase superfamily, such as Ras, Ran, and the Ga subunits of the heterotrimeric
G-proteins. In each of these
proteins, GTP binding, hydrolysis, and exchange regulate, and are regulated by,
binding other macromolecular components of the cell, thereby constituting
elements of the interaction pathways that mediate signal transduction and
assembly.
Publications:
(2006)
Gawronski-Salerno
et al., X-ray structure of the T. aquaticus FtsY:GDP complex suggests
functional roles for the C-terminal helix of the SRP GTPases Proteins In Press.
Focia, et al., Structure of a GDPAlF4 complex of the SRP GTPases Ffh and FtsY, and identification of a peripheral nucleotide interaction site J. Mol. Biol. 360 631-643
(2004)
Focia et
al., Novel Protein
and Mg2+ Configurations in the Mg2+GDP Complex of the SRP GTPase Ffh Proteins 54 222.
Focia, et al., Heterodimeric GTPase core of
the SRP targeting complex (2004) Science 303 373.
(2003)
Shepotinovskaya, et al., Crystallization of the GMPPCP complex of the NG domains of T. aquaticus Ffh and FtsY Acta Cryst. D59 1834.
(2002)
Shepotinovskaya,
et al., Conformational
change of the N-domain accompanies formation of the complex between the GTPase
domains of Thermus aquaticus Ffh and FtsY
Bioch. Biophys. Acta. 1597 92
(2001)
Padmanabhan, et al., The
conformation of bound GMPPNP suggests a mechanism for gating the active
site of the SRP GTPase Structure 9 859.
Keenan, et
al., The Signal
Recognition Particle Annu Rev Biochem 70 755.
(1999)
Freymann, et
al., Functional
changes in the structure of the SRP GTPase on binding GDP and
Mg2+GDP Nature Structural Biology 6 793-801
Grant Support: NIH R01 GM058500