PDBsum entry 1axi

Complex (hormone/receptor)

PDB id: 1axi

Contents

Protein chains

175 a.a. *

191 a.a. *

Ligands

SO4

Waters ×382

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structural plasticity in a remodeled protein-Protein interface.

Authors

S.Atwell, M.Ultsch, A.M.De vos, J.A.Wells.

Ref.

Science, 1997, 278, 1125-1128. [DOI no: 10.1126/science.278.5340.1125]

PubMed id

9353194

Abstract

Remodeling of the interface between human growth hormone (hGH) and the extracellular domain of its receptor was studied by deleting a critical tryptophan residue (at position 104) in the receptor, creating a large cavity, and selecting a pentamutant of hGH by phage display that fills the cavity and largely restores binding affinity. A 2.1 A resolution x-ray structure of the mutant complex showed that the receptor cavity was filled by selected hydrophobic mutations of hGH. Large structural rearrangements occurred in the interface at sites that were distant from the mutations. Such plasticity may be a means for protein-protein interfaces to adapt to mutations as they coevolve.

Figure 1.
Fig. 1. Residues in hGHbp (rendered in pink or orange sticks) that contact hGH (in blue space-filling rendition) in the 1:1 wild-type^ complex (A) or the complex between A1-hGH and W104A-hGHbp (B). Local groups where hydrogen bonds are different between the complexes are shown as yellow dashed lines.

Figure 3.
Fig. 3. Two views (A and B) of nonmutated contact residues that change salt bridge partners in the A1-hGH and W104A-hGHbp complex (right) relative to the wild-type complex (left). Hormone^ residues are in blue, and receptor residues are in pink, except for position 104 which is in orange.

The above figures are reprinted by permission from the AAAs: Science (1997, 278, 1125-1128) copyright 1997.

Secondary reference #1

Title

Human growth hormone and extracellular domain of its receptor: crystal structure of the complex.

Authors

A.M.De vos, M.Ultsch, A.A.Kossiakoff.

Ref.

Science, 1992, 255, 306-312. [DOI no: 10.1126/science.1549776]

PubMed id

1549776