3FL7

Crystal structure of the human ephrin A2 ectodomain

Summary for 3FL7

• Entry DOI: 10.2210/pdb3fl7/pdb
• Related: 1MQB 3C8X 3CZU
• Descriptor: Ephrin receptor, SODIUM ION, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: atp-binding, kinase, nucleotide-binding, receptor, transferase, phosphorylation, transmembrane, tyrosine-protein kinase, glycoprotein, ligand binding domain, cysteine-rich domain, sushi domain, egf-like motif, fibronectin domain, structural genomics consortium, sgc, membrane, phosphoprotein, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 59569.49

Authors

Walker, J.R.,Yermekbayeva, L.,Seitova, A.,Butler-Cole, C.,Bountra, C.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2008-12-18, release date: 2009-01-27, Last modification date: 2024-10-30)

Primary citation

Himanen, J.P.,Yermekbayeva, L.,Janes, P.W.,Walker, J.R.,Xu, K.,Atapattu, L.,Rajashankar, K.R.,Mensinga, A.,Lackmann, M.,Nikolov, D.B.,Dhe-Paganon, S.
Architecture of Eph receptor clusters.
Proc.Natl.Acad.Sci.USA, 107:10860-10865, 2010

PubMed Abstract: Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. Here we present high-resolution structures of the complete EphA2 ectodomain and complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The structures reveal an elongated architecture with novel Eph/Eph interactions, both within and outside of the Eph ligand-binding domain, that suggest the molecular mechanism underlying Eph/ephrin clustering. Structure-function analysis, by using site-directed mutagenesis and cell-based signaling assays, confirms the importance of the identified oligomerization interfaces for Eph clustering.

PubMed: 20505120
DOI: 10.1073/pnas.1004148107

Experimental method

X-RAY DIFFRACTION (2.5 Å)