Allosteric communication between signal peptides and the SecA protein DEAD motor ATPase domain (Journal article)
Baud, C./ Karamanou, S./ Sianidis, G./ Vrontou, E./ Politou, A. S./ Economou, A.
SecA, the preprotein translocase ATPase is built of an amino-terminal DEAD helicase motor domain bound to a regulatory C-domain. SecA recognizes mature and signal peptide preprotein regions. We now demonstrate that the amino-terminal 263 residues of the ATPase subdomain of the DEAD motor are necessary and sufficient for high affinity signal peptide binding. Binding is abrogated by deletion of residues 219-244 that lie within SSD, a novel substrate specificity element of the ATPase subdomain. SSD is essential for protein translocation, is unique to SecA, and is absent from other DEAD proteins. Signal peptide binding to the DEAD motor is controlled in trans by the C-terminal intramolecular regulator of ATPase (IRA1) switch. IRA1 mutations that activate the DEAD motor ATPase also enhance signal peptide affinity. This mechanism coordinates signal peptide binding with ATPase activation. Signal peptide binding causes widespread conformational changes to the ATPase subdomain and inhibits the DEAD motor ATPase. This involves an allosteric mechanism, since binding occurs at sites that are distinct from the catalytic ATPase determinants. Our data reveal the physical determinants and sophisticated intramolecular regulation that allow signal peptides to act as allosteric effectors of the SecA motor.
|Institution and School/Department of submitter:||Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής|
|Keywords:||Adenosine Triphosphatases/*chemistry/metabolism,Allosteric Site,*Bacterial Proteins,Binding Sites,Cross-Linking Reagents/pharmacology,Cytoplasm/metabolism,Escherichia coli Proteins/*chemistry/metabolism,Kinetics,Membrane Transport Proteins/*chemistry/metabolism,Models, Genetic,Mutation,Protein Binding,Protein Conformation,*Protein Sorting Signals,Protein Structure, Tertiary,Recombinant Proteins/metabolism,Surface Plasmon Resonance|
|Appears in Collections:||Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)|
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