PDBsum entry 3dge

Transferase/signaling protein

PDB id: 3dge

Contents

Protein chains

237 a.a. *

122 a.a. *

Ligands

ADP ×2

SO4 ×2

CIT

Waters ×162

* Residue conservation analysis

PDB id:

3dge

Name:

Transferase/signaling protein

Title:

Structure of a histidine kinase-response regulator complex reveals insights into two-component signaling and a novel cis- autophosphorylation mechanism

Structure:

Sensor protein. Chain: a, b. Fragment: cytoplasmic domain, unp residues 232-481. Engineered: yes. Response regulator. Chain: c, d. Engineered: yes

Source:

Thermotoga maritima. Organism_taxid: 2336. Gene: tm_0853. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: tm_0468.

Resolution:

2.80Å R-factor: 0.236 R-free: 0.284

Authors:

P.Casino,A.Marina

Key ref:

P.Casino et al. (2009). Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction. Cell, 139, 325-336. PubMed id: 19800110 DOI: 10.1016/j.cell.2009.08.032

Date:

13-Jun-08 Release date: 07-Jul-09

Protein chains

Q9WZV7  (Q9WZV7_THEMA) -  histidine kinase from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 489 a.a.

Struc: 237 a.a.

Protein chains

Q9WYT9  (Q9WYT9_THEMA) -  Response regulator from Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8)

Seq: 122 a.a.

Struc: 122 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.7.13.3 - histidine kinase.
• Reaction: ATP + protein L-histidine = ADP + protein N-phospho-L-histidine

ATP + protein L-histidine = ADP (Bound ligand (Het Group name = ADP) corresponds exactly) + protein N-phospho-L-histidine

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.cell.2009.08.032

Cell 139:325-336 (2009)

PubMed id: 19800110

Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction.

P.Casino, V.Rubio, A.Marina.

ABSTRACT

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.

Selected figure(s)

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.

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).

The above figures are reprinted by permission from Cell Press: Cell (2009, 139, 325-336) copyright 2009.

Figures were selected by an automated process.