3MX0

Crystal Structure of EphA2 ectodomain in complex with ephrin-A5

Summary for 3MX0

• Entry DOI: 10.2210/pdb3mx0/pdb
• Related PRD ID: PRD_900017
• Descriptor: Ephrin type-A receptor 2, Ephrin-A5, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: ectodomain, receptor-ligand complex, receptor-receptor interaction, transferase receptor-signalling protein complex, transferase receptor/signalling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 124331.22

Authors

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. (deposition date: 2010-05-06, release date: 2010-06-30, 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 (3.506 Å)