PDBsum entry 1lx5

Growth factor/growth factor receptor

PDB id: 1lx5

Contents

Protein chains

104 a.a. *

94 a.a. *

Ligands

NAG-NAG-BMA-MAN-BMA-MAN

NAG ×2

* Residue conservation analysis

PDB id:

1lx5

Name:

Growth factor/growth factor receptor

Title:

Crystal structure of the bmp7/actrii extracellular domain complex

Structure:

Bone morphogenetic protein 7. Chain: a. Synonym: bmp7, osteogenic protein 1, op-1. Engineered: yes. Activin type ii receptor. Chain: b. Fragment: extracellular ligand binding domain, c-terminal truncation. Synonym: actr-ii. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: bmp7. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell: ovary cells. Other_details: dhfr-. Mus musculus.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.30Å R-factor: 0.240 R-free: 0.279

Authors:

J.Greenwald,J.Groppe,W.Kwiatkowski,S.Choe

Key ref:

J.Greenwald et al. (2003). The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly. Mol Cell, 11, 605-617. PubMed id: 12667445 DOI: 10.1016/S1097-2765(03)00094-7

Date:

04-Jun-02 Release date: 01-Apr-03

Protein chain

P18075  (BMP7_HUMAN) -  Bone morphogenetic protein 7 from Homo sapiens

Seq: 431 a.a.

Struc: 104 a.a.

Protein chain

P27038  (AVR2A_MOUSE) -  Activin receptor type-2A from Mus musculus

Seq: 513 a.a.

Struc: 94 a.a.

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.11.30 - receptor protein serine/threonine kinase.
• Reaction:
  1. L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor- protein] + ADP + H⁺
  2. L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor- protein] + ADP + H⁺

L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor- protein] (Bound ligand (Het Group name = NAG) matches with 41.38% similarity) + ADP + H(+)

L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor- protein] (Bound ligand (Het Group name = NAG) matches with 41.38% similarity) + ADP + H(+)

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

reference

DOI no: 10.1016/S1097-2765(03)00094-7

Mol Cell 11:605-617 (2003)

PubMed id: 12667445

The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.

J.Greenwald, J.Groppe, P.Gray, E.Wiater, W.Kwiatkowski, W.Vale, S.Choe.

ABSTRACT

Activins and bone morphogenetic proteins (BMPs) elicit diverse biological responses by signaling through two pairs of structurally related type I and type II receptors. Here we report the crystal structure of BMP7 in complex with the extracellular domain (ECD) of the activin type II receptor. Our structure produces a compelling four-receptor model, revealing that the types I and II receptor ECDs make no direct contacts. Nevertheless, we find that truncated receptors lacking their cytoplasmic domain retain the ability to cooperatively assemble in the cell membrane. Also, the affinity of BMP7 for its low-affinity type I receptor ECD increases 5-fold in the presence of its type II receptor ECD. Taken together, our results provide a view of the ligand-mediated cooperative assembly of BMP and activin receptors that does not rely on receptor-receptor contacts.

Selected figure(s)

Figure 1.
Figure 1. The Structure of the BMP7/ActRII-ECD Complex(A and B) Ribbon diagrams of the BMP7/ActRII-ECD complex (A) with the 2-fold symmetry axis vertical and the membrane facing side at the bottom and (B) the view from above (BMP7, gold and rust; ActRII-ECD, green; cystine sulfurs, yellow space-filling).(C) Stereo view of the interface between BMP7 and ActRII in an orientation close to (A). The residues within 4 Å of the binding partner as well as Glu29 are displayed as balls and sticks. Glu29 and those residues whose mutations are known to affect binding (pink, Figure 2) are labeled.In (A)–(C) significant conformational changes are highlighted (dark blue), and in (C) they are overlaid with the unbound conformations (light blue). This figure was made using MOLSCRIPT (Kraulis, 1991).

Figure 3.
Figure 3. The Model of the BMP7/ActRII/BMPRIa Six-Chain Signaling ComplexBMPRIa (purple) was placed in the complex by aligning the BMP2/BMPRIa structure (Kirsch et al., 2000a) with BMP7.(A) Side view as in Figure 1A is shown as a solvent accessible surface. The horizontal line represents the plane of the membrane.(B) Bottom view (opposite from Figure 1B). Sugars are in black. The C termini are marked with yellow dots and the horizontal distances between them as projected onto the plane of the membrane are 83 Å for type II-type II, 66 Å for type I-type I, and 27 Å and 68 Å for type I-type II. (A) and (B) were prepared with DINO (Philippsen, 2001).(C) Stereo view of ActRII and TGF-βRII bound to their respective ligands overlaid with the BMP2/BMPRIa structure. The BMP7/ActRII complex was aligned as in (A) using the entire ligand. In order to overlay the TGF-βRII binding site (tip of finger 2 on TGF-β3) with BMP2, only 14 residues (86–92 and 98–104 of BMP2) were used for the alignment (Hart et al., 2002). The color scheme is BMP2, white; BMP7, gold; ActRII, green; TGF-β3, blue; TGF-βRII, red; BMPRIa, purple. The receptors and their C termini are labeled.

The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 11, 605-617) copyright 2003.

Figures were selected by an automated process.