Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Functional mimicry of a protein hormone by a peptide agonist: The epo receptor complex at 2.8 Å

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Livnah, O.
  • Stura, E. A.
  • Johnson, D. L.
  • Middleton, S. A.
  • Mulcahy, L. S.
  • Wrighton, N. C.
  • Dower, W. J.
  • Jolliffe, L. K.
  • Wilson, Ian

publication date

  • July 1996

journal

  • Science  Journal

abstract

  • The functional mimicry of a protein by an unrelated small molecule has been a formidable challenge. Now, however, the biological activity of a 166-residue hematopoietic growth hormone, erythropoietin (EPO), with its class 1 cytokine receptor has been mimicked by a 20-residue cyclic peptide unrelated in sequence to the natural ligand. The crystal structure at 2.8 A resolution of a complex of this agonist peptide with the extracellular domain of EPO receptor reveals that a peptide dimer induces an almost perfect twofold dimerization of the receptor. The dimer assembly differs from that of the human growth hormone (hGH) receptor complex and suggests that more than one mode of dimerization may be able to induce signal transduction and cell proliferation. The EPO receptor binding site, defined by peptide interaction, corresponds to the smaller functional epitope identified for hGH receptor. Similarly, the EPO mimetic peptide ligand can be considered as a minimal hormone, and suggests the design of nonpeptidic small molecule mimetics for EPO and other cytokines may indeed be achievable.

subject areas

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design
  • Erythropoietin
  • Growth Hormone
  • Humans
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Sequence Data
  • Peptides, Cyclic
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Secondary
  • Receptors, Erythropoietin
  • Receptors, Somatotropin
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.273.5274.464

PubMed ID

  • 8662530
scroll to property group menus

Additional Document Info

start page

  • 464

end page

  • 471

volume

  • 273

issue

  • 5274

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support