Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors

Autor: Andrey V Tsarev, Milita V Kocharovskaya, Eugene V Loktyushov, Mikhail A. Shulepko, Mikhail P. Kirpichnikov, Zakhar O. Shenkarev, Alexander S. Paramonov, D.S. Kulbatskii, Ekaterina N. Lyukmanova
Rok vydání: 2020
Předmět:
Models
Molecular
Protein Conformation
alpha-Helical
0301 basic medicine
Ly-6/uPAR
Gene Expression
Structural diversity
Receptors
Nicotinic
15N-relaxation
lcsh:Chemistry
0302 clinical medicine
LYNX1
Antigens
Ly
Protein Isoforms
Cloning
Molecular
skin and connective tissue diseases
lcsh:QH301-705.5
Spectroscopy
Chemistry
General Medicine
Nuclear magnetic resonance spectroscopy
Recombinant Proteins
Computer Science Applications
Nicotinic agonist
medicine.anatomical_structure
biological phenomena
cell phenomena
and immunity
Hydrophobic and Hydrophilic Interactions
Protein Binding
Genetic Vectors
backbone dynamics
GPI-Linked Proteins
Antiparallel (biochemistry)
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
NMR spectroscopy
Escherichia coli
medicine
Humans
Protein Interaction Domains and Motifs
Amino Acid Sequence
Physical and Theoretical Chemistry
neoplasms
Nuclear Magnetic Resonance
Biomolecular
Molecular Biology
Adaptor Proteins
Signal Transducing
Acetylcholine receptor
Elapid Venoms
Binding Sites
Sequence Homology
Amino Acid
Neuropeptides
Organic Chemistry
Urokinase-Type Plasminogen Activator
biological factors
Epithelium
enzymes and coenzymes (carbohydrates)
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Heteronuclear molecule
Biophysics
three-finger proteins
Protein Conformation
beta-Strand
nicotinic acetylcholine receptors
Sequence Alignment
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 7280, p 7280 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 19
ISSN: 1422-0067
DOI: 10.3390/ijms21197280
Popis: Ly-6/uPAR or three-finger proteins (TFPs) contain a disulfide-stabilized &beta
structural core and three protruding loops (fingers). In mammals, TFPs have been found in epithelium and the nervous, endocrine, reproductive, and immune systems. Here, using heteronuclear NMR, we determined the three-dimensional (3D) structure and backbone dynamics of the epithelial secreted protein SLURP-1 and soluble domains of GPI-anchored TFPs from the brain (Lynx2, Lypd6, Lypd6b) acting on nicotinic acetylcholine receptors (nAChRs). Results were compared with the data about human TFPs Lynx1 and SLURP-2 and snake &alpha
neurotoxins WTX and NTII. Two different topologies of the &beta
structure were revealed: one large antiparallel &beta
sheet in Lypd6 and Lypd6b, and two &beta
sheets in other proteins. &alpha
Helical segments were found in the loops I/III of Lynx2, Lypd6, and Lypd6b. Differences in the surface distribution of charged and hydrophobic groups indicated significant differences in a mode of TFPs/nAChR interactions. TFPs showed significant conformational plasticity: the loops were highly mobile at picosecond-nanosecond timescale, while the &beta
structural regions demonstrated microsecond-millisecond motions. SLURP-1 had the largest plasticity and characterized by the unordered loops II/III and cis-trans isomerization of the Tyr39-Pro40 bond. In conclusion, plasticity could be an important feature of TFPs adapting their structures for optimal interaction with the different conformational states of nAChRs.
Databáze: OpenAIRE
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