NMR Dynamics of Transmembrane and Intracellular Domains of p75NTR in Lipid-Protein Nanodiscs.
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.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation. Electronic address: mineev@nmr.ru.
Konstantin S
KS
Mineev
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
Sergey A
SA
Goncharuk
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
Pavel K
PK
Kuzmichev
Neurodegeneration Unit, Unidad Funcional de Investigación de Enfermedades Crónicas-Instituto de Salud Carlos III, Madrid, Spain.
Marçal
M
Vilar
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation.
Alexander S
AS
Arseniev
D000595:Amino Acid Sequence; D000818:Animals; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004926:Escherichia coli; D009682:Magnetic Resonance Spectroscopy; D008563:Membrane Lipids / Q000737:chemistry*; D008823:Micelles; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry*; D009419:Nerve Tissue Proteins; D010715:Phosphatidylglycerols / Q000737:chemistry; D051381:Rats; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry* / Q000235:genetics
D008563:Membrane Lipids; D008823:Micelles; D009419:Nerve Tissue Proteins; D010715:Phosphatidylglycerols; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine