Co-operative binding of oxytocin to bovine neurophysin II.
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ABSTRACT:
SUBMITTER: Hope DB
PROVIDER: S-EPMC1165455 | biostudies-other | 1975 May
REPOSITORIES: biostudies-other
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Project description:Simple systems are considered in which the binding of a ligand at a single site exhibits a doubly sigmoid curve when saturation is plotted against the logarithm of ligand concentration, i.e. where a fraction of the site exhibits one dissociation constant and the rest exhibits another. The condition for this to occur is that the ligand should also combine at another site on the binding molecule with comparable affinity and that the binding at one site should markedly lower affinity at the other. The protonation of simple compounds such as cysteine and 3-hydroxypyridine is taken as an example of this process and the equations derived are also applied to the binding of substrates to enzymes.
| S-EPMC1177774 | biostudies-other
Project description:Oxytocin is a short peptide with multiple functions in human biology and has been implicated in autism. We aimed to determine the normal pattern of variation around the oxytocin gene and resequenced it and its flanking regions in 91 individuals from four HapMap populations and one chimpanzee. We identified 14 single nucleotide polymorphisms (SNPs), all noncoding, including eight that were novel. Population genetic analyses were largely consistent with a neutral evolutionary history, but an Hudson-Kreitman-Aguadé (HKA) test revealed more variation within the human population than expected from the level of chimpanzee-human divergence.
| S-EPMC2680061 | biostudies-literature
Project description:1. Rat neurohypophysial extracts have been examined by polyacrylamide-gel electrophoresis. 2. Three of the proteins were tentatively identified as neurophysins by their acidic nature and their disappearance after dehydration of the animals. 3. These proteins were radioactive 24h after intracisternal injection of [(35)S]cysteine. 4. Two of the proteins were present in much greater quantities than the third, and these two were present in the gland in the same ratio as the hormones vasopressin and oxytocin. 5. One of these proteins was absent from glands of rats homozygous for diabetes insipidus but present in heterozygous animals. 6. It is suggested that these two proteins are the vasopressin-neurophysin and oxytocin-neurophysin of the rat.
| S-EPMC1177259 | biostudies-other
Project description:Background Oxytocin plays a salient role that oxytocin plays in contributing to the high levels of human sociality that characterize our species. Curiously, the OXT-Neurophysin I gene has been little studied despite the fact this is the structural gene for the oxytocin nonapeptide. Methods In a large group of National University of Singapore (NUS) Han Chinese undergraduate students we examined four SNPs in the OXT-neurophysin I region. For approximately 1,000 of these students, we also had data on immunogenic plasma oxytocin levels. The students were investigated for several phenotypes relevant to social cognition, including empathy and spirituality. Results Neurophysin I rs3761248 is associated with spirituality, emotional quotient (EQ) and neuroticism. For both spirituality and EQ, there were interactions with gender and the A allele was associated with lower scores for females but with no effect on males, in tune with female-specific findings for autistic-like traits and moderation of the neuro activation of dopaminergic system in the brain. For the personality traits, significant associations were found when POIP was included as a covariate. Both rs3761248 females and males with A alleles scored higher on the met neuroticism measure and lower in agreeableness and conscientiousness. These results suggest that the A allele of rs3761248 is associated with traits that lead that resonate with stress and adverse health, such as high neuroticism, low conscientiousness and agreeableness, as well as low spirituality and low EQ. Conclusions This is the first study showing an association between neurophysin I and human personality traits related to autism.
| S-EPMC5641726 | biostudies-literature
Project description:1. Bovine neurophysin-II contains 1mol of tyrosine residue/10000g of protein. This residue could be readily nitrated with tetranitromethane. On hydrolysis and amino acid analysis 1mol of 3-nitrotyrosine was found/10000g of protein. Starchgel electrophoresis at pH8.5 showed that nitration had converted the native protein into a single, more acidic species. The increase in acidity was consistent with the observed fall in pK of the tyrosine hydroxyl from 9.2 in native neurophysin to 7.3 in the nitrated protein. Further, the absence of any intermediate species, even under conditions of minimum substitution, confirmed that the molecular weight of the monomer is 10000. 2. O-Acetylation of the tyrosine residue was carried out with N-acetylimidazole, in conjunction with the reversible blocking of amino groups by citraconylation. The degree of O-acetylation, determined spectroscopically, was 0.9mol of O-acetyltyrosine/10000g of protein. 3. The hormone-binding ability of modified protein was tested by equilibrium dialysis and was found to be unchanged by either nitration or O-acetylation of the tyrosine residue. 4. Interaction of neurophysin-II and [8-arginine]-vasopressin gave rise to a characteristic difference spectrum with a peak at 286.8nm and shoulder at 279.6nm. Part of this hyperchromicity is thought to result from entry of the tyrosine residue at position 2 in the hormone into the hydrophobic environment of the binding site. With nitrated neurophysin-II a second peak appeared at 436nm, showing that the tyrosine of the protein is also perturbed. The very large red shift (84nm) in this region suggests that the 3-nitrotyrosyl residue not only enters a more hydrophobic environment on protein-hormone interaction, but is caused to ionize more fully by the approach of some positively charged group.
| S-EPMC1185398 | biostudies-other
Project description:1. A third native hormone-binding protein, neurophysin-C, has been isolated from acetone-desiccated bovine pituitary posterior lobes. 2. This protein was detected in lysates of neurosecretory granules isolated from bovine pituitary posterior lobes. 3. The molecular weight appears to be close to 10000. 4. Neurophysin-C is similar in amino acid composition to neurophysin-I and -II; it contains a single residue of tyrosine and of methionine. The N-terminal amino acid in all three neurophysins is alanine. 5. Neurophysin-C accounts for approximately 15% of the total hormone-binding protein present in the pituitary posterior lobes. 6. The new neurophysin forms complexes with oxytocin as well as with [8-arginine]-vasopressin. The complex with vasopressin has been crystallized. 7. Bioassay of the pressor and oxytocic activities of the protein-hormone complexes shows that neurophysin-C binds one molecule of either vasopressin or oxytocin.
| S-EPMC1185126 | biostudies-other
Project description:Current evidence indicates that the ligand-facilitated dimerization of neurophysin is mediated in part by dimerization-induced changes at the hormone binding site of the unliganded state that increase ligand affinity. To elucidate other contributory factors, we investigated the potential role of neurophysin's short interdomain loop (residues 55-59), particularly the effects of loop residue mutation and of deleting amino-terminal residues 1-6, which interact with the loop and adjacent residues 53-54. The neurophysin studied was bovine neurophysin-I, necessitating determination of the crystal structures of des 1-6 bovine neurophysin-I in unliganded and liganded dimeric states, as well as the structure of its liganded Q58V mutant, in which peptide was bound with unexpectedly increased affinity. Increases in dimerization constant associated with selected loop residue mutations and with deletion of residues 1-6, together with structural data, provided evidence that dimerization of unliganded neurophysin-I is constrained by hydrogen bonding of the side chains of Gln58, Ser56, and Gln55 and by amino terminus interactions, loss or alteration of these hydrogen bonds, and probable loss of amino terminus interactions, contributing to the increased dimerization of the liganded state. An additional intersubunit hydrogen bond from residue 81, present only in the liganded state, was demonstrated as the largest single effect of ligand binding directly on the subunit interface. Comparison of bovine neurophysins I and II indicates broadly similar mechanisms for both, with the exception in neurophysin II of the absence of Gln55 side chain hydrogen bonds in the unliganded state and a more firmly established loss of amino terminus interactions in the liganded state. Evidence is presented that loop status modulates dimerization via long-range effects on neurophysin conformation involving neighboring Phe22 as a key intermediary.
| S-EPMC2222833 | biostudies-literature
Project description:Laser nephelometry is a suitable technique for the quantitative determination and differentiation of both lectins and glycoconjugates in the low-picomolar range. Simultaneously this method renders possible investigations on the specificity and mode of interaction between lectins and different ligands. The results demonstrate that the degree of co-operativity between concanavalin A and the respective glycoconjugate is dependent on the presence of hydrophobic binding sites and can be substantially altered by conformational changes of the ligand. The transition from apotransferrin to Fe3+-transferrin induces a transformation of the sigmoidal-shaped binding curve to a hyperbolic one. Hence, at low concentrations, Fe3+-transferrin is bound far better than apotransferrin, whereas maximal binding is nearly identical. After removal of N-acetylneuraminate, concanavalin A is less efficient in differentiating between the Fe3+-charged and Fe3+-free (apo) forms of transferrin.
| S-EPMC1162652 | biostudies-other
Project description:1. The native hormone-binding proteins, neurophysin-I and -II, have been isolated from acetone-desiccated bovine pituitary posterior lobes. 2. Neurophysin-I and -II are present in approximately equal quantities in the tissue and are localized in the neurosecretory granules. 3. The apparent molecular weight, determined by equilibrium sedimentation of neurophysin-I, was 19000 and that of neurophysin-II was 21000; their sedimentation coefficients, S(20,w), were 1.66 and 2.02s respectively. 4. Neurophysin-I and -II are similar in amino acid composition. Neurophysin-II was distinguished from neurophysin-I by the absence of histidine. 5. The proteins form complexes with oxytocin as well as with vasopressin. Complexes of both proteins with [8-arginine]-vasopressin have been crystallized. 6. Bioassay of the pressor and oxytocic activities of the crystals shows that neurophysin-I binds three molecules of either vasopressin or oxytocin whereas neurophysin-II binds only two molecules of each hormone per molecule of protein. Complexes containing two molecules of oxytocin and one molecule of [8-arginine]-vasopressin per molecule of protein are formed by neurophysin-I and -II; both proteins appear to possess three polypeptide-binding sites/molecule.
| S-EPMC1198537 | biostudies-other
Project description:Neurophysin-M, a methionine-containing protein that is the major constituent of neurophysin, has been crystallized as complexes with [8-arginine]-vasopressin. Three moles of vasopressin alone or 2 moles of vasopressin together with 1 mole of oxytocin are bound/mole of protein. An amorphous complex of the protein with oxytocin alone contains 2 moles of the hormone/mole of protein. Deamino-[8-arginine]-vasopressin, a highly active basic analogue of vasopressin, is not bound by neurophysin. The primary amino group of both vasopressin and oxytocin is necessary for binding with neurophysin.
| S-EPMC1198408 | biostudies-other