2BBA

Crystal Structure and Thermodynamic Characterization of the EphB4 Receptor in Complex with an ephrin-B2 Antagonist Peptide Reveals the Determinants for Receptor Specificity.

Summary for 2BBA

• Entry DOI: 10.2210/pdb2bba/pdb
• Descriptor: Ephrin type-B receptor 4, Agonist peptide, SULFATE ION, ... (4 entities in total)
• Functional Keywords: ephb4, tumorigenesis, angiogenesis, peptide mimetics, signaling protein, structural genomics, psi-2, protein structure initiative, accelerated technologies center for gene to 3d structure, atcg3d
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P54760
• Total number of polymer chains: 2
• Total formula weight: 22987.99

Authors

Chrencik, J.E.,Kuhn, P.,Accelerated Technologies Center for Gene to 3D Structure (ATCG3D) (deposition date: 2005-10-17, release date: 2006-07-18, Last modification date: 2024-11-06)

Primary citation

Chrencik, J.E.,Brooun, A.,Recht, M.I.,Kraus, M.L.,Koolpe, M.,Kolatkar, A.R.,Bruce, R.H.,Martiny-Baron, G.,Widmer, H.,Pasquale, E.B.,Kuhn, P.
Structure and thermodynamic characterization of the EphB4/Ephrin-B2 antagonist peptide complex reveals the determinants for receptor specificity.
Structure, 14:321-330, 2006

PubMed Abstract: The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate numerous biological processes in developing and adult tissues and have been implicated in cancer progression and in pathological forms of angiogenesis. We report the crystal structure of the EphB4 receptor in complex with a highly specific antagonistic peptide at a resolution of 1.65 angstroms. The peptide is situated in a hydrophobic cleft of EphB4 corresponding to the cleft in EphB2 occupied by the ephrin-B2 G-H loop, consistent with its antagonistic properties. Structural analysis identifies several residues within the EphB4 binding cleft that likely determine the ligand specificity of this receptor, while isothermal titration calorimetry experiments with truncated forms of the peptide define the amino acid residues of the peptide that are critical for receptor binding. These studies reveal structural features that will aid drug discovery initiatives to develop EphB4 antagonists for therapeutic applications.

PubMed: 16472751
DOI: 10.1016/j.str.2005.11.011

Experimental method

X-RAY DIFFRACTION (1.65 Å)