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Evidence for a novel GTPase priming step in the SRP protein targeting pathway
Author(s) -
Lu Yun,
Qi HaiYan,
Hyndman Janine B.,
Ulbrandt Nancy D.,
Teplyakov Alexey,
Tomasevic Nenad,
Bernstein Harris D.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.23.6724
Subject(s) - signal recognition particle receptor , signal recognition particle , gtpase , biology , protein targeting , microbiology and biotechnology , protein subunit , mutant , transport protein , plasma protein binding , signal peptide , peptide sequence , genetics , membrane protein , gene , membrane
Protein targeting by the signal recognition particle (SRP) pathway requires the interaction of two homologous GTPases that reciprocally regulate each other's GTPase activity, the SRP signal peptide‐ binding subunit (SRP54) and the SRP receptor α‐subunit (SRα). The GTPase domain of both proteins abuts a unique ‘N domain’ that appears to facilitate external ligand binding. To examine the relationship between the unusual regulation and unique architecture of the SRP pathway GTPases, we mutated an invariant glycine in Escherichia coli SRP54 and SRα orthologs (’Ffh‘ and ‘FtsY’, respectively) that resides at the N–GTPase domain interface. A G257A mutation in Ffh produced a lethal phenotype. The mutation did not significantly affect Ffh function, but severely reduced interaction with FtsY. Likewise, mutation of FtsY Gly455 produced growth defects and inhibited interaction with Ffh. The data suggest that Ffh and FtsY interact only in a ‘primed’ conformation which requires interdomain communication. Based on these results, we propose that the distinctive features of the SRP pathway GTPases evolved to ensure that SRP and the SR engage external ligands before interacting with each other.