The Interface between Self-assembling Erythropoietin Receptor Transmembrane Segments Corresponds to a Membrane-spanning Leucine Zipper

Weiming Ruan, Verena Becker, Ursula Klingmüller, Dieter Langosch

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Structural and functional studies recently indicated that the erythropoietin receptor exists as a preassembled homodimer whose activation by ligand binding requires self-interaction of its transmembrane segment. Here, we probed the interface formed by the transmembrane segments by asparagine-scanning mutagenesis in a natural membrane. We show that this interface is based on a leucine zipper-like heptad repeat pattern of amino acids. The strongest impact of asparagine was observed at position 241, suggesting the highest packing density around this position, which is in agreement with results obtained upon mutation to alanine. Interestingly, the same face of the transmembrane helix had previously been shown to enter a heterophilic interaction with the transmembrane segment of gp55-P, a viral membrane protein that leads to ligand-independent receptor activation in infected cells. Further, functional characterization of an erythropoietin receptor mutant with asparagine at position 241 in a hematopoietic cell line showed that this protein could still be activated by erythropoietin yet was not constitutively active. This suggests that forced self-interaction of the transmembrane segments does not suffice to induce signaling of the erythropoietin receptor.

Original languageEnglish (US)
Pages (from-to)3273-3279
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number5
DOIs
StatePublished - Jan 30 2004

Fingerprint

Erythropoietin Receptors
Leucine Zippers
Asparagine
Membranes
Viral Matrix Proteins
Chemical activation
Ligands
Mutagenesis
Erythropoietin
Alanine
Cells
Scanning
Amino Acids
Cell Line
Mutation
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The Interface between Self-assembling Erythropoietin Receptor Transmembrane Segments Corresponds to a Membrane-spanning Leucine Zipper. / Ruan, Weiming; Becker, Verena; Klingmüller, Ursula; Langosch, Dieter.

In: Journal of Biological Chemistry, Vol. 279, No. 5, 30.01.2004, p. 3273-3279.

Research output: Contribution to journalArticle

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