The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor.
Translational initiation factor 2 (IF2) is a guanine nucleotide-binding protein that can bind guanosine 3',5'-(bis) diphosphate (ppGpp), an alarmone involved in stringent response in bacteria. In cells growing under optimal conditions, the GTP concentration is very high, and that of ppGpp very low. However, under stress conditions, the GTP concentration may decline by as much as 50%, and that of ppGpp can attain levels comparable to those of GTP. Here we show that IF2 binds ppGpp at the same nucleotide-binding site and with similar affinity as GTP. Thus, GTP and the alarmone ppGpp can be considered two alternative physiologically relevant IF2 ligands. ppGpp interferes with IF2-dependent initiation complex formation, severely inhibits initiation dipeptide formation, and blocks the initiation step of translation. Our data suggest that IF2 has the properties of a cellular metabolic sensor and regulator that oscillates between an active GTP-bound form under conditions allowing active protein syntheses and an inactive ppGpp-bound form when shortage of nutrients would be detrimental, if not accompanied by slackening of this synthesis.
Milon
Pohl
P
Laboratory of Genetics, Department of Biology MCA, University of Camerino, 62032 Camerino (MC), Italy.
Tischenko
Eugene
E
Tomsic
Jerneja
J
Caserta
Enrico
E
Folkers
Gert
G
La Teana
Anna
A
Rodnina
Marina V
MV
Pon
Cynthia L
CL
Boelens
Rolf
R
Gualerzi
Claudio O
CO
D001665:Binding Sites; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism*; D039881:Prokaryotic Initiation Factor-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary
D008024:Ligands; D009711:Nucleotides; D039881:Prokaryotic Initiation Factor-2; D006160:Guanosine Triphosphate