INVESTIGADORES
MANSILLA Maria Cecilia
artículos
Título:
Structural plasticity and catalysis regulation of a thermosensor histidine kinase
Autor/es:
ALBANESI D; MARTIN, M.; TRAJTENBERG F; MANSILLA MC; HAOUZ A; ALZARI PM; DE MENDOZA D; BUSCHIAZZO A
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Año: 2009 vol. 106 p. 16185 - 16190
ISSN:
0027-8424
Resumen:
Temperature sensing is essential for the survival of living cells. A
major challenge is to understand how a biological thermometer
processes thermal information to optimize cellular functions. Using
structural and biochemical approaches, we show that the thermosensitive
histidine kinase, DesK, from Bacillus subtilis is coldactivated
through specific interhelical rearrangements in its central
four-helix bundle domain. As revealed by the crystal structures of
DesK in different functional states, the plasticity of this helical
domain influences the catalytic activities of the protein, either by
modifying the mobility of the ATP-binding domains for autokinase
activity or by modulating binding of the cognate response regulator
to sustain the phosphotransferase and phosphatase activities.
The structural and biochemical data suggest a model in which
the transmembrane sensor domain of DesK promotes these structural
changes through conformational signals transmitted by the
membrane-connecting two-helical coiled-coil, ultimately controlling
the alternation between output autokinase and phosphatase
activities. The structural comparison of the different DesK variants
indicates that incoming signals can take the form of helix rotations
and asymmetric helical bends similar to those reported for other
sensing systems, suggesting that a similar switching mechanism
could be operational in a wide range of sensor histidine kinases.
Bacillus subtilis is coldactivated
through specific interhelical rearrangements in its central
four-helix bundle domain. As revealed by the crystal structures of
DesK in different functional states, the plasticity of this helical
domain influences the catalytic activities of the protein, either by
modifying the mobility of the ATP-binding domains for autokinase
activity or by modulating binding of the cognate response regulator
to sustain the phosphotransferase and phosphatase activities.
The structural and biochemical data suggest a model in which
the transmembrane sensor domain of DesK promotes these structural
changes through conformational signals transmitted by the
membrane-connecting two-helical coiled-coil, ultimately controlling
the alternation between output autokinase and phosphatase
activities. The structural comparison of the different DesK variants
indicates that incoming signals can take the form of helix rotations
and asymmetric helical bends similar to those reported for other
sensing systems, suggesting that a similar switching mechanism
could be operational in a wide range of sensor histidine kinases.