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Non-specific binding and general cross-reactivity of Y receptor agonists are correlated and should importantly depend on their acidic sectors
- Source :
- Peptides. 32:258-265
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Non-specific binding of Y receptor agonists to intact CHO cells, and to CHO cell or rat brain particulates, is much greater for human neuropeptide Y (hNPY) compared to porcine peptide Y (pPYY), and especially relative to human pancreatic polypeptide (hPP). This binding of hNPY is reduced by alkali cations in preference to non-ionic chaotrope urea, while the much lower non-specific binding of pPYY is more sensitive to urea. The difference could mainly be due to the 10-16 stretch in 36-residue Y agonists (residues 8-14 in N-terminally clipped 34-peptides), located in the sector that contains all acidic residues of physiological Y agonists. Anionic pairs containing aspartate in the 10-16 zone could be principally responsible for non-specific attachments, but may also aid the receptor site binding. Two such pairs are found in hNPY, one in pPYY, and none in hPP. The hydroxyl amino acid residue at position 13 in mammalian PYY and PP molecules could lower conformational plasticity and the non-selective binding via intrachain hydrogen bonding. The acidity of this tract could also be important in agonist selectivity of the Y receptor subtypes. The differences point to an evolutionary reduction of promiscuous protein binding from NPY to PP, and should also be important for Y agonist selectivity within NPY receptor group, and correlate with partial agonism and out-of group cross-reactivity with other receptors.
- Subjects :
- Physiology
Peptide Hormones
Amino Acid Motifs
Sus scrofa
Peptide
Plasma protein binding
Biochemistry
Protein Structure, Secondary
Mice
Endocrinology
Protein structure
Cricetinae
Urea
Neuropeptide Y
Receptor
Cerebral Cortex
chemistry.chemical_classification
Perchlorates
Chemistry
Neuropeptide Y receptor
Sodium Compounds
Protein Binding
Agonist
medicine.drug_class
Stereochemistry
Detergents
Molecular Sequence Data
CHO Cells
Pancreatic Polypeptide
Transfection
Article
Gastrointestinal Hormones
Cellular and Molecular Neuroscience
Cricetulus
medicine
Animals
Humans
Peptide YY
Amino Acid Sequence
Binding site
Binding Sites
Cell Membrane
Neuropeptides
Peptide Fragments
Rats
Receptors, Neuropeptide Y
HEK293 Cells
Ultracentrifugation
Subjects
Details
- ISSN :
- 01969781
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Peptides
- Accession number :
- edsair.doi.dedup.....dd49a54ba0c8d23267972499e68dd105