PDBsum entry 4bk4

Signaling protein

PDB id: 4bk4

Contents

Protein chains

514 a.a.

300 a.a.

PDB id:

4bk4

Name:

Signaling protein

Title:

Crystal structure of the human epha4 ectodomain

Structure:

Ephrin type-a receptor 4. Chain: a, b. Fragment: hepha4 ectodomain, residues 20-547. Synonym: eph-like kinase 8, ek8, hek8, tyrosine-protein kinase tyro1, tyrosine-protein kinase receptor sek. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t.

Resolution:

3.65Å R-factor: 0.351 R-free: 0.386

Authors:

E.Seiradake,A.Schaupp,D.Del Toro Ruiz,R.Kaufmann,N.Mitakidis, K.Harlos,A.R.Aricescu,R.Klein,E.Y.Jones

Key ref:

E.Seiradake et al. (2013). Structurally encoded intraclass differences in EphA clusters drive distinct cell responses. Nat Struct Biol, 20, 958-964. PubMed id: 23812375 DOI: 10.1038/nsmb.2617

Date:

22-Apr-13 Release date: 03-Jul-13

Protein chain

P54764  (EPHA4_HUMAN) -  Ephrin type-A receptor 4 from Homo sapiens

Seq: 986 a.a.

Struc: 514 a.a.

Protein chain

P54764  (EPHA4_HUMAN) -  Ephrin type-A receptor 4 from Homo sapiens

Seq: 986 a.a.

Struc: 300 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1038/nsmb.2617

Nat Struct Biol 20:958-964 (2013)

PubMed id: 23812375

Structurally encoded intraclass differences in EphA clusters drive distinct cell responses.

E.Seiradake, A.Schaupp, D.del Toro Ruiz, R.Kaufmann, N.Mitakidis, K.Harlos, A.R.Aricescu, R.Klein, E.Y.Jones.

ABSTRACT

Functional outcomes of ephrin binding to Eph receptors (Ephs) range from cell repulsion to adhesion. Here we used cell collapse and stripe assays, showing contrasting effects of human ephrinA5 binding to EphA2 and EphA4. Despite equivalent ligand binding affinities, EphA4 triggered greater cell collapse, whereas EphA2-expressing cells adhered better to ephrinA5-coated surfaces. Chimeric receptors showed that the ectodomain is a major determinant of cell response. We report crystal structures of EphA4 ectodomain alone and in complexes with ephrinB3 and ephrinA5. These revealed closed clusters with a dimeric or circular arrangement in the crystal lattice, contrasting with extended arrays previously observed for EphA2 ectodomain. Localization microscopy showed that ligand-stimulated EphA4 induces smaller clusters than does EphA2. Mutant Ephs link these characteristics to interactions observed in the crystal lattices, suggesting a mechanism by which distinctive ectodomain surfaces determine clustering, and thereby signaling, properties.