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PDBsum entry 3dge
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Transferase/signaling protein
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PDB id
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3dge
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References listed in PDB file
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Key reference
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Title
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Structural insight into partner specificity and phosphoryl transfer in two-Component signal transduction.
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Authors
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P.Casino,
V.Rubio,
A.Marina.
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Ref.
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Cell, 2009,
139,
325-336.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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The chief mechanism used by bacteria for sensing their environment is based on
two conserved proteins: a sensor histidine kinase (HK) and an effector response
regulator (RR). The signal transduction process involves highly conserved
domains of both proteins that mediate autokinase, phosphotransfer, and
phosphatase activities whose output is a finely tuned RR phosphorylation level.
Here, we report the structure of the complex between the entire cytoplasmic
portion of Thermotoga maritima class I HK853 and its cognate, RR468, as well as
the structure of the isolated RR468, both free and BeF(3)(-) bound. Our results
provide insight into partner specificity in two-component systems, recognition
of the phosphorylation state of each partner, and the catalytic mechanism of the
phosphatase reaction. Biochemical analysis shows that the HK853-catalyzed
autokinase reaction proceeds by a cis autophosphorylation mechanism within the
HK subunit. The results suggest a model for the signal transduction mechanism in
two-component systems.
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Figure 1.
Figure 1. Crystal Structure of the HK853[CP]-RR468 Complex
and Expanded Views of the Contacts within the Complex
(A
and B) Ribbon diagrams of the complex viewed from the cell
membrane along the twofold axis (indicated with a black ellipse)
(A) or perpendicularly to this axis (B), with the cell membrane
and the cell interior at the top and bottom, respectively. The
α helices of each HK protomer are colored blue (HK853[CP]) and
cyan (HK853[CP]^*), and the two RR468 molecules are shown in
gold (RR468) and light yellow (RR468^*), although β strands are
colored red in all cases. In (B), the RR468 molecule at the back
has been omitted for clarity. The side chains of the
phosphoacceptor H260 and D53 residues and the bound sulfate and
ADPβN molecules are illustrated in stick representation. In one
protomer of each HK853[CP] and RR468, secondary structure
elements and relevant loops have been labeled.
(C)
Six-helix bundle formed by the DHp domains of the two HK853[CP]
subunits (blue and cyan, and abbreviated HK) and by the α1
helices of both RR468 molecules (red and magenta, and
abbreviated RR). The orientation is similar to that in (B). Loop
β5-α5 is also shown for the RR molecule in the front.
(D)
Interactions between the β3-α3 loop of RR468 and the ATP lid
and β4-α4 loop of the CA domain of HK853, to illustrate the
interposition of the ATP lid between the secluded nucleotide and
His260 of the same subunit.
(E) Interactions of the RR468
β4-α4 loop (green) with the DHp-CA interdomain linker (cyan).
Side chains of interacting residues are shown with broken lines
indicating polar bonds.
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Figure 6.
Figure 6. Signal Transduction Model
In the model, the
signal reaches the catalytic core of the HK via helix α1
rotation. This rotation modifies DHp packing and the position of
the associated CA domain. The latter domain either approaches
the phosphoacceptor His, triggering the autokinase reaction
(center), or moves away to generate the appropriate docking
surfaces for either the interaction with nonphosphorylated RR,
promoting phosphotransfer (right), or the interaction with the P
 vert,
similar RR, promoting dephosphorylation (left).
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2009,
139,
325-336)
copyright 2009.
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