PROTEIN TARGETING Paired GTPs Holding Things Together

Proteins destined for secretion, or for incorporation into membranes, contain a signal sequence that binds to the signal recognition particle (SRP), which then forms a complex with its receptor (SR). Dissociation of the complex, and release of the nascent polypeptide to a membrane translocation pore, depends on the reciprocally stimulatory guanosine triphosphatase (GTPase) activity of the SRP and SR. Egea et al. used x-ray crystallography and mutagenic analysis to study the interaction of Ffh, a core component of the bacterial SRP, and FtsY, the bacterial SR, in the presence of a nonhydrolyzable analog of GTP. Ffh and FtsY formed a heterodimer with an extensive interface stabilized by numerous bonding interactions surrounding a symmetrical active site containing the two nucleotides. The two nucleotides were aligned head to toe so that the phosphate of one GTP could hydrogen bond with the 3' OH of the ribose ring of the other. The authors used various nucleotide analogs to verify that this OH was critical for FtsY-Ffh association and for their reciprocal stimulation of GTPase activity. The ensuing hydrolysis of GTP, by releasing the phosphate, disrupts the interaction and thereby leads to dissociation of the complex and delivery of the nascent polypeptide.

P. F. Egea, S. Shan, J. Napetschnig, D. F. Savage, P. Walter, R. M. Stroud, Substrate twinning activates the signal recognition particle and its receptor. Nature 427, 215-221 (2004). [Online Journal]