PDBsum entry 2uzy

Signaling protein/receptor

PDB id: 2uzy

Contents

Protein chains

286 a.a. *

630 a.a. *

* Residue conservation analysis

PDB id:

2uzy

Name:

Signaling protein/receptor

Title:

Structure of the human receptor tyrosine kinase met in complex with the listeria monocytogenes invasion protein inlb: low resolution, crystal form ii

Structure:

Internalin b. Chain: a, c. Fragment: internalin domain (cap, lrr, ir)\: inlb321, residues 36- 321. Synonym: inlb. Engineered: yes. Hepatocyte growth factor receptor. Chain: b, d. Fragment: sema, psi, ig1, ig2\: met741, residues 25-740.

Source:

Listeria monocytogenes. Organism_taxid: 169963. Strain: egd-e. Variant: serovar 12a. Expressed in: escherichia coli. Expression_system_taxid: 469008. Homo sapiens. Human. Organism_taxid: 9606.

Resolution:

4.00Å R-factor: 0.251 R-free: 0.301

Authors:

H.H.Niemann,V.Jager,P.J.G.Butler,J.Van Den Heuvel,S.Schmidt, D.Ferraris,E.Gherardi,D.W.Heinz

Key ref:

H.H.Niemann et al. (2007). Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. Cell, 130, 235-246. PubMed id: 17662939 DOI: 10.1016/j.cell.2007.05.037

Date:

02-May-07 Release date: 07-Aug-07

Protein chains

P0DQD2  (INLB_LISMO) -  Internalin B from Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)

Seq: 630 a.a.

Struc: 286 a.a.*

Protein chains

P08581  (MET_HUMAN) -  Hepatocyte growth factor receptor from Homo sapiens

Seq: 1390 a.a.

Struc: 630 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains B, D: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

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

Added reference

DOI no: 10.1016/j.cell.2007.05.037

Cell 130:235-246 (2007)

PubMed id: 17662939

Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB.

H.H.Niemann, V.Jäger, P.J.Butler, J.van den Heuvel, S.Schmidt, D.Ferraris, E.Gherardi, D.W.Heinz.

ABSTRACT

The tyrosine kinase Met, the product of the c-met proto-oncogene and the receptor for hepatocyte growth factor/scatter factor (HGF/SF), mediates signals critical for cell survival and migration. The human pathogen Listeria monocytogenes exploits Met signaling for invasion of host cells via its surface protein InlB. We present the crystal structure of the complex between a large fragment of the human Met ectodomain and the Met-binding domain of InlB. The concave face of the InlB leucine-rich repeat region interacts tightly with the first immunoglobulin-like domain of the Met stalk, a domain which does not bind HGF/SF. A second contact between InlB and the Met Sema domain locks the otherwise flexible receptor in a rigid, signaling competent conformation. Full Met activation requires the additional C-terminal domains of InlB which induce heparin-mediated receptor clustering and potent signaling. Thus, although it elicits a similar cellular response, InlB is not a structural mimic of HGF/SF.

Selected figure(s)

Figure 3.
Figure 3. Flexibility of the Free Met Ectodomain versus Rigidity of the Complex with InlB[321]
(A) Overlay of the Met[741]-InlB[321] complex (coloring as in Figure 2) with Met[567] from the complex with the HGF/SF β chain (pink). The structures were aligned on the PSI domain to visualize the large relative rearrangement of the Sema domain.
(B) Overlay of the Met-InlB complex from crystal form I (coloring as in Figure 2) and from crystal form II (pink). The structures were aligned on InlB. The Met Ig1 and PSI domains and the InlB-proximal side of the Sema domain align very well. The secondary interface between the InlB IR and the Met Sema domain is preserved.

Figure 4.
Figure 4. The Primary Interface between InlB LRR and Met Ig1
(A) The InlB LRR embraces only the top of Met Ig1 with the unusual β-wing of the long B-C loop. The LRRs are numbered, and the strands in Ig1 are labeled. Exposed aromatic side chains at the concave face of the InlB LRR and the disulfide bond connecting strands D and E of Met Ig1 are shown as sticks.
(B) Close-up showing InlB Y170^i and Y214^i interacting with K599^M and K600^M of Met. Y170^i makes hydrogen bonds (dotted orange lines) to the carbonyl of K599^M and the R602^M side chain. The side chains of K599^M and K600^M are held in place by an intra- and intermolecular salt bridge (dotted purple lines), respectively.
(C) Side chains of residues from β strands C, F, and G of the Met Ig1 domain form a hydrophobic pocket into which W124^i from the concave face of the InlB LRR binds.
(D) Electrostatic potential of InlB[321] (left) and Met (right; Ig2 omitted). In the open-book view, the surfaces involved in binding are shown for both proteins. The negative charges (red) on the InlB LRR face positive charges (blue) on Met Ig1.

The above figures are reprinted by permission from Cell Press: Cell (2007, 130, 235-246) copyright 2007.

Figures were selected by an automated process.