Abstract
SecA is a helicase-like motor that couples ATP hydrolysis with the translocation of extracytoplasmic protein substrates. As in most helicases, this process is thought to occur through nucleotide-regulated rigid-body movement of the motor domains. NMR, thermodynamic and biochemical data show that SecA uses a novel mechanism wherein conserved regions lining the nucleotide cleft undergo cycles of disorder-order transitions while switching among functional catalytic states. The transitions are regulated by interdomain interactions mediated by crucial 'arginine finger' residues located on helicase motifs. Furthermore, we show that the nucleotide cleft allosterically communicates with the preprotein substrate-binding domain and the regulatory, membrane-inserting C domain, thereby allowing for the coupling of the ATPase cycle to the translocation activity. The intrinsic plasticity and functional disorder-order folding transitions coupled to ligand binding seem to provide a precise control of the catalytic activation process and simple regulation of allosteric mechanisms.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 594-602 |
| Number of pages | 9 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 13 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
Cite this
Disorder-order folding transitions underlie catalysis in the helicase motor of SecA. / Keramisanou, Dimitra; Biris, Nikolaos; Gelis, Ioannis; Sianidis, Georgios; Karamanou, Spyridoula; Economou, Anastassios; Kalodimos, Charalampos G.
In: Nature Structural and Molecular Biology, Vol. 13, No. 7, 07.2006, p. 594-602.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disorder-order folding transitions underlie catalysis in the helicase motor of SecA
AU - Keramisanou, Dimitra
AU - Biris, Nikolaos
AU - Gelis, Ioannis
AU - Sianidis, Georgios
AU - Karamanou, Spyridoula
AU - Economou, Anastassios
AU - Kalodimos, Charalampos G.
PY - 2006/7
Y1 - 2006/7
N2 - SecA is a helicase-like motor that couples ATP hydrolysis with the translocation of extracytoplasmic protein substrates. As in most helicases, this process is thought to occur through nucleotide-regulated rigid-body movement of the motor domains. NMR, thermodynamic and biochemical data show that SecA uses a novel mechanism wherein conserved regions lining the nucleotide cleft undergo cycles of disorder-order transitions while switching among functional catalytic states. The transitions are regulated by interdomain interactions mediated by crucial 'arginine finger' residues located on helicase motifs. Furthermore, we show that the nucleotide cleft allosterically communicates with the preprotein substrate-binding domain and the regulatory, membrane-inserting C domain, thereby allowing for the coupling of the ATPase cycle to the translocation activity. The intrinsic plasticity and functional disorder-order folding transitions coupled to ligand binding seem to provide a precise control of the catalytic activation process and simple regulation of allosteric mechanisms.
AB - SecA is a helicase-like motor that couples ATP hydrolysis with the translocation of extracytoplasmic protein substrates. As in most helicases, this process is thought to occur through nucleotide-regulated rigid-body movement of the motor domains. NMR, thermodynamic and biochemical data show that SecA uses a novel mechanism wherein conserved regions lining the nucleotide cleft undergo cycles of disorder-order transitions while switching among functional catalytic states. The transitions are regulated by interdomain interactions mediated by crucial 'arginine finger' residues located on helicase motifs. Furthermore, we show that the nucleotide cleft allosterically communicates with the preprotein substrate-binding domain and the regulatory, membrane-inserting C domain, thereby allowing for the coupling of the ATPase cycle to the translocation activity. The intrinsic plasticity and functional disorder-order folding transitions coupled to ligand binding seem to provide a precise control of the catalytic activation process and simple regulation of allosteric mechanisms.
UR - http://www.scopus.com/inward/record.url?scp=33745863903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745863903&partnerID=8YFLogxK
U2 - 10.1038/nsmb1108
DO - 10.1038/nsmb1108
M3 - Article
C2 - 16783375
AN - SCOPUS:33745863903
VL - 13
SP - 594
EP - 602
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 7
ER -