Crystal structure of an ephrin ectodomain.
Eph receptor tyrosine kinases and their membrane-associated ligands, the ephrins, are essential regulators of axon guidance, cell migration, segmentation, and angiogenesis. There are two classes of vertebrate ephrin ligands which have distinct binding specificities for their cognate receptors. Multimerization of the ligands is required for receptor activation, and ephrin ligands themselves signal intracellularly upon binding Eph receptors. We have determined the structure of the extracellular domain of mouse ephrin-B2. The ephrin ectodomain is an eight-stranded beta barrel with topological similarity to plant nodulins and phytocyanins. Based on the structure, we have identified potential surface determinants of Eph/ephrin binding specificity and a ligand dimerization region. The high sequence similarity among ephrin ectodomains indicates that all ephrins may be modeled upon the ephrin-B2 structure presented here.
Toth
J
J
Boston Biomedical Research Institute, Watertown, Massachusetts 02472, USA.
Cutforth
T
T
Gelinas
A D
AD
Bethoney
K A
KA
Bard
J
J
Harrison
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D003461:Crystallography; D036388:Ephrin-B2; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010940:Plant Proteins / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
D036388:Ephrin-B2; D008024:Ligands; D008565:Membrane Proteins; D010940:Plant Proteins; C045625:nodulin