7RGF

Protocadherin gammaC4 EC1-4 crystal structure disrupted trans interface

Summary for 7RGF

• Entry DOI: 10.2210/pdb7rgf/pdb
• Descriptor: Protocadherin gamma C4, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]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, ... (9 entities in total)
• Functional Keywords: cadherin, cell-surface receptor, neuronal self-avoidance, cell adhesion
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 98921.00

Authors

Goodman, K.M.,Mannepalli, S.,Honig, B.,Shapiro, L. (deposition date: 2021-07-15, release date: 2022-03-16, Last modification date: 2024-10-23)

Primary citation

Goodman, K.M.,Katsamba, P.S.,Rubinstein, R.,Ahlsen, G.,Bahna, F.,Mannepalli, S.,Dan, H.,Sampogna, R.V.,Shapiro, L.,Honig, B.
How clustered protocadherin binding specificity is tuned for neuronal self-/nonself-recognition.
Elife, 11:-, 2022

PubMed Abstract: The stochastic expression of fewer than 60 clustered protocadherin (cPcdh) isoforms provides diverse identities to individual vertebrate neurons and a molecular basis for self-/nonself-discrimination. cPcdhs form chains mediated by alternating and interactions between apposed membranes, which has been suggested to signal self-recognition. Such a mechanism requires that cPcdh dimers form promiscuously to generate diverse recognition units, and that interactions have precise specificity so that isoform mismatches terminate chain growth. However, the extent to which cPcdh interactions fulfill these requirements has not been definitively demonstrated. Here, we report biophysical experiments showing that cPcdh interactions are promiscuous, but with preferences favoring formation of heterologous dimers. homophilic interactions are remarkably precise, with no evidence for heterophilic interactions between different isoforms. A new C-type cPcdh crystal structure and mutagenesis data help to explain these observations. Overall, the interaction characteristics we report for cPcdhs help explain their function in neuronal self-/nonself-discrimination.

PubMed: 35253643
DOI: 10.7554/eLife.72416

Experimental method

X-RAY DIFFRACTION (2.4 Å)