Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2

Juha Pekka Himanen, Mark Henkemeyer, Dimitar B. Nikolov

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The Eph receptors, which bind a group of cell-membrane-anchored ligands known as ephrins, represent the largest subfamily of receptor tyrosine kinases (RTKs). They are predominantly expressed in the developing and adult nervous system and are important in contact-mediated axon guidance, axon fasciculation and cell migration. Eph receptors are unique among other RTKs in that they fall into two subclasses with distinct ligand specificities, and in that they can themselves function as ligands to activate bidirectional cell-cell signalling. We report here the crystal structure at 2.9 Å resolution of the amino-terminal ligand-binding domain of the EphB2 receptor (also known as Nuk). The domain folds into a compact jellyroll β-sandwich composed of 11 antiparallel β-strands. Using structure-based mutagenesis, we have identified an extended loop that is important for ligand binding and class specificity. This loop, which is conserved within but not between EpH RTK subclasses, packs against the concave β-sandwich surface near positions at which missense mutations cause signalling defects, localizing the ligand- binding region on the surface of the receptor.

Original languageEnglish (US)
Pages (from-to)486-491
Number of pages6
JournalNature
Volume396
Issue number6710
DOIs
StatePublished - Dec 3 1998

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EphB2 Receptors
Receptor Protein-Tyrosine Kinases
Ligands
Eph Family Receptors
Ephrins
Missense Mutation
Mutagenesis
Nervous System
Cell Movement
Cell Membrane

ASJC Scopus subject areas

  • General

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Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2. / Himanen, Juha Pekka; Henkemeyer, Mark; Nikolov, Dimitar B.

In: Nature, Vol. 396, No. 6710, 03.12.1998, p. 486-491.

Research output: Contribution to journalArticle

Himanen, Juha Pekka ; Henkemeyer, Mark ; Nikolov, Dimitar B. / Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2. In: Nature. 1998 ; Vol. 396, No. 6710. pp. 486-491.
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