7S7K

Crystal structure of the EphB2 extracellular domain

Summary for 7S7K

• Entry DOI: 10.2210/pdb7s7k/pdb
• Descriptor: Ephrin type-B receptor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: ephb2, ecd, autoinhibitory, transferase
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 59673.58

Authors

Xu, Y.,Xu, K.,Nikolov, D.B. (deposition date: 2021-09-16, release date: 2021-10-27, Last modification date: 2024-11-13)

Primary citation

Xu, Y.,Robev, D.,Saha, N.,Wang, B.,Dalva, M.B.,Xu, K.,Himanen, J.P.,Nikolov, D.B.
The Ephb2 Receptor Uses Homotypic, Head-to-Tail Interactions within Its Ectodomain as an Autoinhibitory Control Mechanism.
Int J Mol Sci, 22:-, 2021

PubMed Abstract: The Eph receptor tyrosine kinases and their ephrin ligands direct axon pathfinding and neuronal cell migration, as well as mediate many other cell-cell communication events. Their dysfunctional signaling has been shown to lead to various diseases, including cancer. The Ephs and ephrins both localize to the plasma membrane and, upon cell-cell contact, form extensive signaling assemblies at the contact sites. The Ephs and the ephrins are divided into A and B subclasses based on their sequence conservation and affinities for each other. The molecular details of Eph-ephrin recognition have been previously revealed and it has been documented that ephrin binding induces higher-order Eph assemblies, which are essential for full biological activity, via multiple, distinct Eph-Eph interfaces. One Eph-Eph interface type is characterized by a homotypic, head-to-tail interaction between the ligand-binding and the fibronectin domains of two adjacent Eph molecules. While the previous Eph ectodomain structural studies were focused on A class receptors, we now report the crystal structure of the full ectodomain of EphB2, revealing distinct and unique head-to-tail receptor-receptor interactions. The EphB2 structure and structure-based mutagenesis document that EphB2 uses the head-to-tail interactions as a novel autoinhibitory control mechanism for regulating downstream signaling and that these interactions can be modulated by posttranslational modifications.

PubMed: 34638814
DOI: 10.3390/ijms221910473

Experimental method

X-RAY DIFFRACTION (3.15 Å)