PDBsum entry: 1ktz

Cytokine/cytokine receptor

PDB id: 1ktz

Contents

Protein chains

82 a.a. *

106 a.a. *

Waters ×163

* Residue conservation analysis

PDB id:

1ktz

Name:

Cytokine/cytokine receptor

Title:

Crystal structure of the human tgf-beta type ii receptor extracellular domain in complex with tgf-beta3

Structure:

Transforming growth factor beta 3. Chain: a. Synonym: tgf-beta3. Engineered: yes. Tgf-beta type ii receptor. Chain: b. Fragment: extracellular domain. Synonym: tbr-2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562

Biol. unit:

Dimer (from PDB file)

Resolution:

2.15Å R-factor: 0.201 R-free: 0.215

Authors:

P.J.Hart,S.Deep,A.B.Taylor,Z.Shu,C.S.Hinck,A.P.Hinck

Key ref:

P.J.Hart et al. (2002). Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex. Nat Struct Biol, 9, 203-208. PubMed id: 11850637 DOI: 10.1038/nsb766

Date:

18-Jan-02 Release date: 27-Feb-02

Protein chain

P10600  (TGFB3_HUMAN) -  Transforming growth factor beta-3

Seq: 412 a.a.

Struc: 82 a.a.

Protein chain

P37173  (TGFR2_HUMAN) -  TGF-beta receptor type-2

Seq: 567 a.a.

Struc: 106 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.11.30 - Receptor protein serine/threonine kinase.
• Reaction: ATP + [receptor-protein] = ADP + [receptor-protein] phosphate

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

 Gene Ontology (GO) functional annotation 

• Cellular component: membrane (1 term)
• Biological process: protein amino acid phosphorylation (1 term)
• Biochemical function: growth factor activity (4 terms)

Added reference

DOI no: 10.1038/nsb766

Nat Struct Biol 9:203-208 (2002)

PubMed id: 11850637

Crystal structure of the human TbetaR2 ectodomain--TGF-beta3 complex.

P.J.Hart, S.Deep, A.B.Taylor, Z.Shu, C.S.Hinck, A.P.Hinck.

ABSTRACT

Transforming growth factor-beta (TGF-beta) is the prototype of a large family of structurally related cytokines that play key roles in maintaining cellular homeostasis by signaling through two classes of functionally distinct Ser/Thr kinase receptors, designated as type I and type II. TGF-beta initiates receptor assembly by binding with high affinity to the type II receptor. Here, we present the 2.15 A crystal structure of the extracellular ligand-binding domain of the human TGF-beta type II receptor (ecTbetaR2) in complex with human TGF-beta3. ecTbetaR2 interacts with homodimeric TGF-beta3 by binding identical finger segments at opposite ends of the growth factor. Relative to the canonical 'closed' conformation previously observed in ligand structures across the superfamily, ecTbetaR2-bound TGF-beta3 shows an altered arrangement of its monomeric subunits, designated the 'open' conformation. The mode of TGF-beta3 binding shown by ecTbetaR2 is compatible with both ligand conformations. This, in addition to the predicted mode for TGF-beta binding to the type I receptor ectodomain (ecTbetaR1), suggests an assembly mechanism in which ecTbetaR1 and ecTbetaR2 bind at adjacent positions on the ligand surface and directly contact each other via protein--protein interactions.

Selected figure(s)

Figure 1.
Figure 1. Structure of the (ecT R2)[2]−TGF- 3 complex. a, Side view of the complex, with two ecT R2 molecules (green) and the two TGF- 3 monomers (blue and red). The TGF- 3 interchain disulfide bond is shown in black. The major secondary structural elements, as determined by the DSSP algorithm^42, and chain termini are labeled. b, Stereo view of ecT R2 (green) superimposed with ecActR2 (pink). The four ecT R2 disulfide bonds structurally equivalent to those in ecActR2 — 28-61, 54-78, 98-113 and 115-120 — are shown in blue. The two disulfides present within ecT R2 loop 1 (L1), 31-48 and 38-44, but not in ecActR2 are shown in red. The one disulfide present within ecActR2, 66-85, but not ecT R2 is shown in black. Side chains of the three ecT R2 residues at the interface with TGF- 3, Leu 27, Ile 53 and Glu 119, are shown in black. 4 designates -strand 4 that binds in the cleft between the TGF- 3 fingertips. ecActR2 residues that comprise the putative interface with activin, Phe 42, Trp 60 and Phe 83, are shown in red. ecT R2 loop 4 (L4) packs against the surface of the central -sheet, decreasing the accessibility of ecT R2 residues structurally equivalent to ecActR2 Phe 42, Trp 60 and Phe 83. c, Structural differences between bound and free TGF- 3. ecT R2-bound (blue and red monomers) and free (magenta and tan monomers) TGF- 3 homodimer structures are depicted by the left and right images, respectively. Shown within a single monomer are the 'fingertips' and the BMP type IA and putative type II receptor binding epitopes, designated as the 'wrist' and 'knuckle', respectively. For clarity, the 'thumb' epitope is shown on the symmetry-related monomer. d, Comparison of the free and bound TGF- 3 homodimer structures, in which the structures have been aligned by maximizing the alignment between the blue monomer of the bound form and the magenta monomer of the free form (1.1 Å root mean square (r.m.s.) deviation). Relative to the second monomer of free TGF- 3 (tan), the second monomer of the ecT R2-bound form (red) is rotated 101° around the axis shown.

Figure 3.
Figure 3. Contacts at the (ecT R2)[2]−TGF- 3 interface. a, Stereo view of the ecT R2−TGF- 3 interface in which the backbone and side chains of ecT R2 and TGF- 3 are green and blue, respectively. Disulfide bonds are black. Amino acid side chains are labeled according to the their residue numbers. b, Stereo view of the hydrogen-bonded ion pair between ecT R2 Asp 32 and TGF- 3 Arg 94. ecT R2 backbone and side chains are depicted in green; TGF- 3, in blue; and the interfacial water molecules, by red spheres. The [A]-weighted^44 electron density, with coefficients 2mF[o] - DF[c], is contoured at 1.1 . c, The molecular interaction surfaces of ecT R2 (top) and TGF- 3 (bottom). The molecules are color coded according to the electrostatic potential and are contoured at 25 kT. The interaction surfaces are defined by pairs of charged amino acids that lie at the periphery of their binding sites: Glu 119 and Asp 32 in ecT R2, and Arg 25 and Arg 94 in TGF- 3. In the complex, ecT R2 Asp 32 pairs with TGF- 3 Arg 94, and ecT R2 Glu 119 pairs with TGF- 3 Arg 25, as indicated by the arrows.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 203-208) copyright 2002.

Figures were selected by an automated process.