Allosteric regulation of SecA: magnesium-mediated control of conformation and activity.
In bacteria, the SecA protein associates with a ubiquitous protein channel SecYEG where it drives the post-translational secretion of pre-proteins across the plasma membrane. The high-resolution structures of both proteins have been determined in their resting states; however, the mechanism that couples ATP hydrolysis to active transport of substrate proteins through the membrane is not well understood. An analysis of the steady-state ATPase activity of the enzyme reveals that there is an allosteric binding site for magnesium distinct from that associated with hydrolysis of ATP. We have demonstrated that this regulation involves a large conformational change to the SecA dimer, which exerts a strong influence on the turnover and affinity for ATP, as well as the affinity for ADP. The strong inhibitory influence of magnesium on the ATPase activity can be countered by cardiolipin and conditions that promote protein translocation.
Gold
Vicki A M
VA
Department of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
Robson
Alice
A
Clarke
Anthony R
AR
Collinson
Ian
I
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002308:Cardiolipins / Q000378:metabolism; D019281:Dimerization; D029968:Escherichia coli Proteins / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011498:Protein Precursors / Q000378:metabolism; D020836:Protein Structure, Quaternary; D000069816:SEC Translocation Channels; D000081416:SecA Proteins
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002308:Cardiolipins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D011498:Protein Precursors; D000069816:SEC Translocation Channels; C057184:outer membrane protein A precursor (E coli); D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins; D008274:Magnesium