NMR Dynamics of Transmembrane and Intracellular Domains of p75NTR in Lipid-Protein Nanodiscs

作者：Mineev, Konstantin S.^*; Goncharuk, Sergey A.; Kuzmichev, Pavel K.; Vilar, Marcal; Arseniev, Alexander S.

来源：Biophysical Journal, 2015, 109(4): 772-782.

DOI：10.1016/j.bpj.2015.07.009

• MEMBRANE-ACTIVE PEPTIDES
• PHOSPHOLIPID-BILAYER NANODISCS
• SMALL-MOLECULE MODULATION
• NEUROTROPHIN RECEPTOR
• CELL-DEATH
• BACKBONE DYNAMICS
• P75(NTR)
• SYSTEM
• DEGENERATION
• RELAXATION

P75NTR is a type I integral membrane protein that plays a key role in neurotrophin signaling. However, structural data for the receptor in various functional states are sparse and controversial. In this work, we studied the spatial structure and mobility of the transmembrane and intracellular parts of p75NTR, incorporated into lipid-protein nanodiscs of various sizes and compositions, by solution NMR spectroscopy. Our data reveal a high level of flexibility and disorder in the juxtamembrane chopper domain of p75NTR, which results in the motions of the receptor death domain being uncoupled from the motions of the transmembrane helix. Moreover, none of the intracellular domains of p75NTR demonstrated a propensity to interact with the membrane or to self-associate under the experimental conditions. The obtained data are discussed in the context of the receptor activation mechanism.

• 出版日期2015-8-18