5LKN

NMR solution structure of human FNIII domain 2 of NCAM

5LKN の概要

• エントリーDOI: 10.2210/pdb5lkn/pdb
• NMR情報: BMRB: 34026
• 分子名称: Neural cell adhesion molecule 1 (1 entity in total)
• 機能のキーワード: fibronectin type iii domain, protein interactions, cell adhesion
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11858.32

構造登録者

Slapsak, U.,Salzano, G.,Amin, L.,Abskharon, R.N.N.,Ilc, G.,Zupancic, B.,Biljan, I.,Plavec, J.,Giachin, G.,Legname, G. (登録日: 2016-07-22, 公開日: 2016-09-14, 最終更新日: 2024-06-19)

主引用文献

Slapsak, U.,Salzano, G.,Amin, L.,Abskharon, R.N.,Ilc, G.,Zupancic, B.,Biljan, I.,Plavec, J.,Giachin, G.,Legname, G.
The N Terminus of the Prion Protein Mediates Functional Interactions with the Neuronal Cell Adhesion Molecule (NCAM) Fibronectin Domain.
J.Biol.Chem., 291:21857-21868, 2016

PubMed Abstract: The cellular form of the prion protein (PrP) 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. PrP 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 PrP 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 PrP (HuPrP) and NCAM interaction using stimulated emission depletion (STED) nanoscopy, SPR, and NMR spectroscopy approaches. PrP co-localizes with NCAM in mouse hippocampal neurons, and this interaction is mainly mediated by the intrinsically disordered PrP 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 PrP N terminus as a dynamic and functional element responsible for protein-protein interaction.

PubMed: 27535221
DOI: 10.1074/jbc.M116.743435

実験手法

SOLUTION NMR