PDBsum entry 1hwg

Complex (hormone/receptor)

PDB id: 1hwg

Contents

Protein chains

184 a.a. *

194 a.a. *

Waters ×175

* Residue conservation analysis

PDB id:

1hwg

Name:

Complex (hormone/receptor)

Title:

1:2 complex of human growth hormone with its soluble binding protein

Structure:

Growth hormone. Chain: a. Engineered: yes. Growth hormone binding protein. Chain: b, c. Fragment: extracellular domain. Engineered: yes. Other_details: one hormone with two receptor molecules

Source:

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

Biol. unit:

Homo-Dimer (from PDB file)

Resolution:

2.50Å R-factor: 0.199 R-free: 0.287

Authors:

S.M.Sundstrom,T.Lundqvist

Key ref:

M.Sundström et al. (1996). Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution. J Biol Chem, 271, 32197-32203. PubMed id: 8943276 DOI: 10.1074/jbc.271.50.32197

Date:

13-Nov-96 Release date: 19-Nov-97

Protein chain

P01241  (SOMA_HUMAN) -  Somatotropin from Homo sapiens

Seq: 217 a.a.

Struc: 184 a.a.

Protein chains

P10912  (GHR_HUMAN) -  Growth hormone receptor from Homo sapiens

Seq: 638 a.a.

Struc: 194 a.a.

DOI no: 10.1074/jbc.271.50.32197

J Biol Chem 271:32197-32203 (1996)

PubMed id: 8943276

Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution.

M.Sundström, T.Lundqvist, J.Rödin, L.B.Giebel, D.Milligan, G.Norstedt.

ABSTRACT

Human growth hormone binds two receptor molecules and thereby induces signal transduction through receptor dimerization. At high concentrations, growth hormone acts as an antagonist because of a large difference in affinities at the respective binding sites. This antagonist action can be enhanced further by reducing binding in the low affinity binding site. A growth hormone antagonist mutant Gly-120 --> Arg, has been crystallized with its receptor as a 1:1 complex and the crystal structure determined at 2.9 A resolution. The 1:1 complex is remarkably similar to the native growth hormone-receptor 1:2 complex. A comparison between the two structures reveals only minimal differences in the conformations of the hormone or its receptor in the two complexes, including the angle between the two immunoglobulin-like domains of the receptor. Further, two symmetry-related 1:1 complexes in the crystal form a 2:2 complex with a large solvent inaccessible area between two receptor molecules. In addition, we present here a native human growth hormone-human growth hormone-binding protein 1:2 complex structure at 2.5 A resolution. One important difference between our structure and the previously published crystal structure at 2.8 A is revealed. Trp-104 in the receptor, a key residue in the hormone-receptor interaction, has an altered conformation in the low affinity site enabling a favorable hydrogen bond to be formed with Asp-116 of the hormone.

Selected figure(s)

Figure 1.
Fig. 1. Schematic representation of the general architecture of the 1:2 complex. The two receptor molecules are in red (high affinity) and yellow (low affinity). The picture was generated^ using MOLSCRIPT (36) and raster3D (37).

Figure 4.
Fig. 4. Planar stacking of hydrophobic and Arg/Lys residues in domain 2 of the binding protein. The 2F[o]F[c]^ electron density map of the 1:2 complex is contoured at 1.0.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (1996, 271, 32197-32203) copyright 1996.

Figures were selected by an automated process.