Pro4 prolyl peptide bond isomerization in human galectin-7 modulates the monomer-dimer equilibrum to affect function

Autor: Irina V. Nesmelova, Herbert Kaltner, Hans-Joachim Gabius, Aurelio J. Dregni, Vladimir A. Daragan, Malwina Michalak, Jürgen Kopitz, Michelle C. Miller, Hans Ippel, Kevin H. Mayo
Přispěvatelé: Biochemie, RS: Carim - B01 Blood proteins & engineering
Jazyk: angličtina
Rok vydání: 2020
Předmět:
STRUCTURAL BASIS
Immunology & Inflammation
Magnetic Resonance Spectroscopy
Stereochemistry
p53-induced gene-1
Galectins
Biophysics
Glycobiology
PROTEIN
Peptide
Biochemistry
NEUROBLASTOMA-CELL-GROWTH
03 medical and health sciences
CHEMICAL-SHIFT ASSIGNMENTS
NMR spectroscopy
Isomerism
Structural Biology
Cell Line
Tumor
SURFACE BINDING
Peptide bond
Humans
Binding site
Molecular Biology
Conformational isomerism
Research Articles
030304 developmental biology
Molecular switch
chemistry.chemical_classification
n-15 backbone
0303 health sciences
Binding Sites
Hydrogen bond
030302 biochemistry & molecular biology
apoptosis
Cell Biology
Nuclear magnetic resonance spectroscopy
toxin b-subunit
molecular dynamics
chemistry
concanavalin-a
NMR relaxation
lectin
site-directed mutagenesis
Protein Multimerization
Isomerization
squamous-cell
Zdroj: Biochemical Journal
Biochemical Journal, 477(17), 3147-3165. Portland Press Ltd.
ISSN: 0264-6021
Popis: Human galectin-7 (Gal-7; also termed p53-induced gene 1 product) is a multifunctional effector by productive pairing with distinct glycoconjugates and protein counter-receptors in the cytoplasm and nucleus, as well as on the cell surface. Its structural analysis by NMR spectroscopy detected doubling of a set of particular resonances, an indicator of Gal-7 existing in two conformational states in slow exchange on the chemical shift time scale. Structural positioning of this set of amino acids around the P4 residue and loss of this phenomenon in the bioactive P4L mutant indicated cis–trans isomerization at this site. Respective resonance assignments confirmed our proposal of two Gal-7 conformers. Mapping hydrogen bonds and considering van der Waals interactions in molecular dynamics simulations revealed a structural difference for the N-terminal peptide, with the trans-state being more exposed to solvent and more mobile than the cis-state. Affinity for lactose or glycan-inhibitable neuroblastoma cell surface contact formation was not affected, because both conformers associated with an overall increase in order parameters (S2). At low µM concentrations, homodimer dissociation is more favored for the cis-state of the protein than its trans-state. These findings give direction to mapping binding sites for protein counter-receptors of Gal-7, such as Bcl-2, JNK1, p53 or Smad3, and to run functional assays at low concentration to test the hypothesis that this isomerization process provides a (patho)physiologically important molecular switch for Gal-7.
Databáze: OpenAIRE
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