Identification and characterization of peptides that bind the PPIase domain of Parvulin17

Abstract

Peptidyl-prolyl cis-trans isomerases (PPIases) are the enzymes that increase the rate of isomerization of the peptide bond N-terminal to the proline substrate. Par14 and its isoform Par17 belong to the Parvulin family of PPIases. Par14 can bind AT-rich double-stranded DNA and was shown to be part of the pre-ribosomal ribonucleoprotein (pre-rRNP) complexes, where it functions as an RNA processing factor that is involved in ribosome biogenesis. Its longer isoform Par17 is expressed only in cells of hominids, where it is targeted to the mitochondria. To find binding partners (peptides or proteins) for Par17, we applied the phage display technology. We panned 7-mer and 12-mer peptide libraries against Par17. The consensus sequence XHSXVHØ, where X can be any amino acid and Ø is a hydrophobic amino acid, was enriched from both libraries. We demonstrate the binding of this motif to the PPIase domain of Par17 using phage ELISA and NMR spectroscopy. We propose that residues Met90, Val91, Phe94, Gln95, Glu96, and Ala98 of Par17 are involved in substrate recognition, and that the phage display-selected motif XHSXVHØ can be recognized by Par17 PPIase domain in vivo.

Molecular Determination of mirRNA-126 rs4636297, Phosphoinositide-3-Kinase Regulatory Subunit 1-Gene Variability rs7713645, rs706713 (Tyr73Tyr), rs3730089 (Met326Ile) and Their Association with Susceptibility to T2D

“…Future longitudinal studies with larger sample sizes and in different populations to examine the effects of both the miR-126 SNP and one or more PIKR risk alleles on susceptibility to T2D, T2D complications and lipid metabolism are strongly recommended. In addition, further-protein protein interactions studies using the techniques such as yeast-two hybrid, phage display, x-ray crystallography, protein NMR spectroscopy [ 38 , 40 , 41 , 42 , 43 ] are required to examine the effect of SNPs in PI3KR1 gene on the PI3K structure, function and interaction with other proteins.…”

Association of Genetic and Allelic Variants of Von Willebrand Factor (VWF), Glutathione S-Transferase and Tumor Necrosis Factor Alpha with Ischemic Stroke Susceptibility and Progression in the Saudi Population

“…The VWF rs61748511 T > C SNP (VWF c.3445T > C p.Cys1149 Arg) may result in drastic changes, since the sulfur-containing amino acid cysteine (Cys) 1149 is replaced by the positively charged amino acid arginine (Arg) ( Figure 1 ). The influence of this gene variant on the VWF is yet to be investigated in protein functional and protein–protein interaction (PPI) studies [ 40 , 41 , 42 , 43 ]. This SNP has been reported to be associated with von Willebrand Disease in a Pakistani population [ 27 ].…”

Effect of pH on Diclofenac–Lysozyme Interaction: Structural and Functional Aspect

“…Proteins are versatile molecules and perform many different functions in the human body. They are flexible molecules, and ligand binding can affect their hydrodynamics and function; these alterations can be harmful or useful ( Babu et al, 2011 ; Elfaki et al, 2013 ; Ajmal et al, 2017a ). Drug binding to transport proteins can significantly affect the metabolism of drug molecules.…”