Structural basis of mechanochemical coupling in a hexameric molecular motor

Denis E Kainov, Erika J Mancini, Jelena Telenius, Jiri Lisal, Jonathan M Grimes, Dennis H Bamford, David I Stuart, Roman Tuma

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

The P4 protein of bacteriophage phi 12 is a hexameric molecular motor closely related to superfamily 4 helicases. P4 converts chemical energy from ATP hydrolysis into mechanical work, to translocate single-stranded RNA into a viral capsid. The molecular basis of mechanochemical coupling, i.e. how small similar to 1 angstrom changes in the ATP-binding site are amplified into nanometer scale motion along the nucleic acid, is not understood at the atomic level. Here we study in atomic detail the mechanochemical coupling using structural and biochemical analyses of P4 mutants. We show that a conserved region, consisting of superfamily 4 helicase motifs H3 and H4 and loop L2, constitutes the moving lever of the motor. The lever tip encompasses an RNA-binding site that moves along the mechanical reaction coordinate. The lever is flanked by gamma-phosphate sensors (Asn-234 and Ser-252) that report the nucleotide state of neighboring subunits and control the lever position. Insertion of an arginine finger (Arg-279) into the neighboring catalytic site is concomitant with lever movement and commences ATP hydrolysis. This ensures cooperative sequential hydrolysis that is tightly coupled to mechanical motion. Given the structural conservation, the mutated residues may play similar roles in other hexameric helicases and related molecular motors.
Alkuperäiskielienglanti
LehtiJournal of Biological Chemistry
Vuosikerta283
Numero6
Sivut3607- 3617
Sivumäärä11
ISSN0021-9258
DOI - pysyväislinkit
TilaJulkaistu - 2008
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 118 Biotieteet

Lainaa tätä

Kainov, Denis E ; Mancini, Erika J ; Telenius, Jelena ; Lisal, Jiri ; Grimes, Jonathan M ; Bamford, Dennis H ; Stuart, David I ; Tuma, Roman. / Structural basis of mechanochemical coupling in a hexameric molecular motor. Julkaisussa: Journal of Biological Chemistry. 2008 ; Vuosikerta 283, Nro 6. Sivut 3607- 3617.
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title = "Structural basis of mechanochemical coupling in a hexameric molecular motor",
abstract = "The P4 protein of bacteriophage phi 12 is a hexameric molecular motor closely related to superfamily 4 helicases. P4 converts chemical energy from ATP hydrolysis into mechanical work, to translocate single-stranded RNA into a viral capsid. The molecular basis of mechanochemical coupling, i.e. how small similar to 1 angstrom changes in the ATP-binding site are amplified into nanometer scale motion along the nucleic acid, is not understood at the atomic level. Here we study in atomic detail the mechanochemical coupling using structural and biochemical analyses of P4 mutants. We show that a conserved region, consisting of superfamily 4 helicase motifs H3 and H4 and loop L2, constitutes the moving lever of the motor. The lever tip encompasses an RNA-binding site that moves along the mechanical reaction coordinate. The lever is flanked by gamma-phosphate sensors (Asn-234 and Ser-252) that report the nucleotide state of neighboring subunits and control the lever position. Insertion of an arginine finger (Arg-279) into the neighboring catalytic site is concomitant with lever movement and commences ATP hydrolysis. This ensures cooperative sequential hydrolysis that is tightly coupled to mechanical motion. Given the structural conservation, the mutated residues may play similar roles in other hexameric helicases and related molecular motors.",
keywords = "118 Biological sciences",
author = "Kainov, {Denis E} and Mancini, {Erika J} and Jelena Telenius and Jiri Lisal and Grimes, {Jonathan M} and Bamford, {Dennis H} and Stuart, {David I} and Roman Tuma",
year = "2008",
doi = "10.1074/jbc.M706366200",
language = "English",
volume = "283",
pages = "3607-- 3617",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology",
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}

Kainov, DE, Mancini, EJ, Telenius, J, Lisal, J, Grimes, JM, Bamford, DH, Stuart, DI & Tuma, R 2008, 'Structural basis of mechanochemical coupling in a hexameric molecular motor', Journal of Biological Chemistry, Vuosikerta 283, Nro 6, Sivut 3607- 3617. https://doi.org/10.1074/jbc.M706366200

Structural basis of mechanochemical coupling in a hexameric molecular motor. / Kainov, Denis E; Mancini, Erika J; Telenius, Jelena; Lisal, Jiri; Grimes, Jonathan M; Bamford, Dennis H; Stuart, David I; Tuma, Roman.

julkaisussa: Journal of Biological Chemistry, Vuosikerta 283, Nro 6, 2008, s. 3607- 3617.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Structural basis of mechanochemical coupling in a hexameric molecular motor

AU - Kainov, Denis E

AU - Mancini, Erika J

AU - Telenius, Jelena

AU - Lisal, Jiri

AU - Grimes, Jonathan M

AU - Bamford, Dennis H

AU - Stuart, David I

AU - Tuma, Roman

PY - 2008

Y1 - 2008

N2 - The P4 protein of bacteriophage phi 12 is a hexameric molecular motor closely related to superfamily 4 helicases. P4 converts chemical energy from ATP hydrolysis into mechanical work, to translocate single-stranded RNA into a viral capsid. The molecular basis of mechanochemical coupling, i.e. how small similar to 1 angstrom changes in the ATP-binding site are amplified into nanometer scale motion along the nucleic acid, is not understood at the atomic level. Here we study in atomic detail the mechanochemical coupling using structural and biochemical analyses of P4 mutants. We show that a conserved region, consisting of superfamily 4 helicase motifs H3 and H4 and loop L2, constitutes the moving lever of the motor. The lever tip encompasses an RNA-binding site that moves along the mechanical reaction coordinate. The lever is flanked by gamma-phosphate sensors (Asn-234 and Ser-252) that report the nucleotide state of neighboring subunits and control the lever position. Insertion of an arginine finger (Arg-279) into the neighboring catalytic site is concomitant with lever movement and commences ATP hydrolysis. This ensures cooperative sequential hydrolysis that is tightly coupled to mechanical motion. Given the structural conservation, the mutated residues may play similar roles in other hexameric helicases and related molecular motors.

AB - The P4 protein of bacteriophage phi 12 is a hexameric molecular motor closely related to superfamily 4 helicases. P4 converts chemical energy from ATP hydrolysis into mechanical work, to translocate single-stranded RNA into a viral capsid. The molecular basis of mechanochemical coupling, i.e. how small similar to 1 angstrom changes in the ATP-binding site are amplified into nanometer scale motion along the nucleic acid, is not understood at the atomic level. Here we study in atomic detail the mechanochemical coupling using structural and biochemical analyses of P4 mutants. We show that a conserved region, consisting of superfamily 4 helicase motifs H3 and H4 and loop L2, constitutes the moving lever of the motor. The lever tip encompasses an RNA-binding site that moves along the mechanical reaction coordinate. The lever is flanked by gamma-phosphate sensors (Asn-234 and Ser-252) that report the nucleotide state of neighboring subunits and control the lever position. Insertion of an arginine finger (Arg-279) into the neighboring catalytic site is concomitant with lever movement and commences ATP hydrolysis. This ensures cooperative sequential hydrolysis that is tightly coupled to mechanical motion. Given the structural conservation, the mutated residues may play similar roles in other hexameric helicases and related molecular motors.

KW - 118 Biological sciences

U2 - 10.1074/jbc.M706366200

DO - 10.1074/jbc.M706366200

M3 - Article

VL - 283

SP - 3607

EP - 3617

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 6

ER -