Naslov
The N-terminus of the Prion Protein Mediates Functional Interactions with NCAM Fibronectin Domain

Autori
Slapšak, Urška ; Salzano, Giulia ; Amin, Ladan ; Abskharon, Romany N.N. ; Ilc, Gregor ; Zupančič, Blaž ; Biljan, Ivana ; Plavec, Janez ; Giachin, Gabriele ; Legname, Giuseppe

Izvornik
The Journal of biological chemistry (0021-9258) 291 (2016); 21857-21868

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Prion protein ; NCAM ; Fibronectin type-3 domain ; protein-protein interaction ; stimulated emission depletion (STED) microscopy ; NMR spectroscopy

Sažetak
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 signalling 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, surface plasma resonance (SPR) and NMR spectroscopy approaches. PrPC co-localizes with NCAM in mouse hyppocampal neurons and this interaction is mainly mediated by the intrinsically disordered PrPC N-terminal tail, which binds with high affinity to NCAM Fibronectin type-3 domain. NMR structural investigations revealed surface interacting epitopes governing the interaction between HuPrP N-terminus and the second module of NCAM Fibronectin type-3 domain. Our data provided molecular details about the interaction between HuPrP and NCAM Fibronectin domain, and revealed a new role of PrPC N-terminus as a dynamic and functional element responsible for protein-protein interaction.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA