The N Terminus of the Prion Protein Mediates Functional Interactions with the Neuronal Cell Adhesion Molecule (NCAM) Fibronectin Domain
| Autor: | Ivana Biljan, Giulia Salzano, Gabriele Giachin, Blaž Zupančič, Giuseppe Legname, Urška Slapšak, Gregor Ilc, Janez Plavec, Romany Abskharon, Ladan Amin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Scaffold protein Cell signaling animal diseases Settore BIO/09 - Fisiologia Biochemistry Hippocampus protein-protein interaction NCAM NMR spectroscopy STED cell adhesion fibronectin fibronectin type-3 domain nuclear magnetic resonance (NMR) prion prion protein stimulated emission depletion microscopy Animals Humans Mice Neural Cell Adhesion Molecules Neurons Nuclear Magnetic Resonance Biomolecular PrPC Proteins Protein Domains Mammals Transmissible spongiform encephalopathy biology Neurodegenerative diseases Cell biology Structural investigation Protein Structure and Folding Stimulated emission Gene isoform Protein-protein interactions Cells Nuclear Magnetic Resonance Biomolecules Cell adhesion Cell membranes Cytology Molecules Nuclear magnetic resonance spectroscopy Proteins Functional interaction Peripheral nervous system Scaffolding proteins Stimulated emission depletion Structural determinants Transmissible spongiform encephalopathies Scaffolds (biology) Protein–protein interaction 03 medical and health sciences medicine Molecular Biology Cell Biology medicine.disease nervous system diseases Fibronectin 030104 developmental biology nervous system biology.protein Neural cell adhesion molecule Neuronal Cell Adhesion Molecule Biomolecular |
| Zdroj: | The Journal of biological chemistry. 291(42) |
| ISSN: | 1083-351X |
| Popis: | The cellular form of the prion protein (PrPC) is a highly conserved glycoprotein mostly expressed in the central and peripheral nervous systems by different cell types in mammals. A misfolded, pathogenic isoform, denoted as prion, is related to a class of neurodegenerative diseases known as transmissible spongiform encephalopathy. PrPC function has not been unequivocally clarified, and it is rather defined as a pleiotropic protein likely acting as a dynamic cell surface scaffolding protein for the assembly of different signaling modules. Among the variety of PrPC protein interactors, the neuronal cell adhesion molecule (NCAM) has been studied in vivo, but the structural basis of this functional interaction is still a matter of debate. Here we focused on the structural determinants responsible for human PrPC (HuPrP) and NCAM interaction using stimulated emission depletion (STED) nanoscopy, SPR, and NMR spectroscopy approaches. PrPC co-localizes with NCAM in mouse hippocampal neurons, and this interaction is mainly mediated by the intrinsically disordered PrPC N-terminal tail, which binds with high affinity to the NCAM fibronectin type-3 domain. NMR structural investigations revealed surface-interacting epitopes governing the interaction between HuPrP N terminus and the second module of the NCAM fibronectin type-3 domain. Our data provided molecular details about the interaction between HuPrP and the NCAM fibronectin domain, and revealed a new role of PrPC N terminus as a dynamic and functional element responsible for protein-protein interaction. |
| Databáze: | OpenAIRE |
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