1EBP

COMPLEX BETWEEN THE EXTRACELLULAR DOMAIN OF ERYTHROPOIETIN (EPO) RECEPTOR [EBP] AND AN AGONIST PEPTIDE [EMP1]

Summary for 1EBP

• Entry DOI: 10.2210/pdb1ebp/pdb
• Descriptor: EPO RECEPTOR, EPO MIMETICS PEPTIDE 1 (2 entities in total)
• Functional Keywords: erythropoietin receptor, signal transduction, protein minimization, drug design, cytokine receptor class 1, complex (cytokine receptor-peptide), complex (cytokine receptor-peptide) complex, complex (cytokine receptor/peptide)
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein. Isoform EPOR-S: Secreted: P19235
• Total number of polymer chains: 4
• Total formula weight: 50849.69

Authors

Livnah, O.,Stura, E.A.,Wilson, I.A. (deposition date: 1996-05-07, release date: 1997-07-29, Last modification date: 2024-10-30)

Primary citation

Livnah, O.,Stura, E.A.,Johnson, D.L.,Middleton, S.A.,Mulcahy, L.S.,Wrighton, N.C.,Dower, W.J.,Jolliffe, L.K.,Wilson, I.A.
Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 A.
Science, 273:464-471, 1996

PubMed 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.

PubMed: 8662530

Experimental method

X-RAY DIFFRACTION (2.8 Å)