8A16

Human PTPRM domains FN3-4, in spacegroup P212121

Summary for 8A16

• Entry DOI: 10.2210/pdb8a16/pdb
• Descriptor: Receptor-type tyrosine-protein phosphatase mu, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: receptor phosphatase, homophilic dimer, cell adhesion
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 59768.34

Authors

Caroe, E.,Graham, S.C.,Sharpe, H.J.,Deane, J.E. (deposition date: 2022-05-31, release date: 2023-03-15, Last modification date: 2024-10-23)

Primary citation

Hay, I.M.,Shamin, M.,Caroe, E.R.,Mohammed, A.S.A.,Svergun, D.I.,Jeffries, C.M.,Graham, S.C.,Sharpe, H.J.,Deane, J.E.
Determinants of receptor tyrosine phosphatase homophilic adhesion: Structural comparison of PTPRK and PTPRM extracellular domains.
J.Biol.Chem., 299:102750-102750, 2023

PubMed Abstract: Type IIB receptor protein tyrosine phosphatases are cell surface transmembrane proteins that engage in cell adhesion via their extracellular domains (ECDs) and cell signaling via their cytoplasmic phosphatase domains. The ECDs of type IIB receptor protein tyrosine phosphatases form stable, homophilic, and trans interactions between adjacent cell membranes. Previous work has demonstrated how one family member, PTPRM, forms head-to-tail homodimers. However, as the interface was composed of residues conserved across the family, the determinants of homophilic specificity remain unknown. Here, we have solved the X-ray crystal structure of the membrane-distal N-terminal domains of PTPRK that form a head-to-tail dimer consistent with intermembrane adhesion. Comparison with the PTPRM structure demonstrates interdomain conformational differences that may define homophilic specificity. Using small-angle X-ray scattering, we determined the solution structures of the full-length ECDs of PTPRM and PTPRK, identifying that both are rigid extended molecules that differ in their overall long-range conformation. Furthermore, we identified one residue, W351, within the interaction interface that differs between PTPRM and PTPRK and showed that mutation to glycine, the equivalent residue in PTPRM, abolishes PTPRK dimer formation in vitro. This comparison of two members of the receptor tyrosine phosphatase family suggests that homophilic specificity is driven by a combination of shape complementarity and specific but limited sequence differences.

PubMed: 36436563
DOI: 10.1016/j.jbc.2022.102750

Experimental method

X-RAY DIFFRACTION (2.89 Å)