5ZRX

Crystal Structure of EphA2/SHIP2 Complex

Summary for 5ZRX

• Entry DOI: 10.2210/pdb5zrx/pdb
• Descriptor: Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2,Ephrin type-A receptor 2 (2 entities in total)
• Functional Keywords: sam domain, heterodimer, signaling protein, cell signaling, receptor, transmembrane, tyrosine-protein kinase, cell adhesion, protein binding
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cell membrane ; Single-pass type I membrane protein : Q03145
• Total number of polymer chains: 2
• Total formula weight: 35243.34

Authors

Wang, Y.,Shang, Y.,Li, J.,Chen, W.,Li, G.,Wan, J.,Liu, W.,Zhang, M. (deposition date: 2018-04-25, release date: 2018-05-30, Last modification date: 2023-11-22)

Primary citation

Wang, Y.,Shang, Y.,Li, J.,Chen, W.,Li, G.,Wan, J.,Liu, W.,Zhang, M.
Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions.
Elife, 7:-, 2018

PubMed Abstract: The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here, we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases.

PubMed: 29749928
DOI: 10.7554/eLife.35677

Experimental method

X-RAY DIFFRACTION (1.5 Å)