Topic
Melanocortin receptor binding
About: Melanocortin receptor binding is a research topic. Over the lifetime, 19 publications have been published within this topic receiving 460 citations.
Papers
TL;DR: The structure suggests that A GRP possesses an additional melanocortin-receptor contact region within a loop formed by the first 16 residues of its C-terminal domain that confers AGRP's distinct selectivity for MC3R and MC4R.
Abstract: The agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic (appetite-stimulating) activity. The cysteine-rich C-terminal domain of this protein, corresponding to AGRP(87−132), contains five disulfide bonds and exhibits receptor binding affinity and antagonism equivalent to that of the full-length protein. The three-dimensional structure of this domain has been determined by 1H NMR at 800 MHz. The first 34 residues of AGRP(87−132) are well-ordered and contain a three-stranded antiparallel β sheet, where the last two strands form a β hairpin. The relative spatial positioning of the disulfide cross-links demonstrates that the ordered region of AGRP(87−132) adopts the inhibitor cystine knot (ICK) fold previously identified for numerous invertebrate toxins. Interestingly, this may be the first example of a mammalian protein assigned to the ICK superfamily. The hairpin's turn region presents a triplet of resi...
98 citations
TL;DR: Differences that were observed between the engineered proteins indicate the importance of the structural scaffold and the amino acids neighbouring the grafted peptide sequences.
Abstract: Disintegrins represent a group of disulfide-rich peptides ranging in size from 41 to over 80 residues and are antagonists of several integrin receptors. Disintegrins containing an RGD or KGD sequence are potent inhibitors of platelet aggregation as they block the binding of fibrinogen to alpha(IIb)beta(3) integrin. The high affinity binding to alpha(IIb)beta(3) in comparison to short linear peptides has been attributed to the localisation of the RGD or KGD sequence within a defined three-dimensional structure. Cystine knot microproteins are members of another family of small disulfide-rich peptides that consist of only 28-40 amino acid residues. They display numerous biological activities depending on the peptide sequence of loop regions that are fixed on a structural scaffold that is stabilised by three knot-forming disulfide bonds. In the present study we grafted RGD and KGD containing peptide sequences with seven and 11 amino acids, respectively, into two cystine knot microproteins, the trypsin inhibitor EETI-II and the melanocortin receptor binding domain of the human agouti-related protein AGRP, as well as into the small disintegrin obtustatin. The engineered proteins were much more potent to inhibit the fibrinogen binding, alpha(IIb)beta(3) activation and platelet aggregation when compared to the grafted peptides. Differences that were observed between the engineered proteins indicate the importance of the structural scaffold and the amino acids neighbouring the grafted peptide sequences.
86 citations
TL;DR: The robust expression of MC receptor protein in spinal cord regions that are generally associated with nociception suggests a potentially broader involvement of endogenous melanocortins in spinal pathways which mediate the responses to peripheral injury, in addition to any direct melanoc Cortin effects on sprouting and neurite outgrowth.
78 citations
TL;DR: Novel inhibitors of the AGRP/MC4 binding based on (piperazinylethyl)piperazines were prepared, and their structure-activity relationship was established.
Abstract: Agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin action.1 In the hypothalamus, melanocortin peptide agonists act as satiety-inducing factors that mediate their action t...
54 citations
TL;DR: The data indicate that the His residue of the small rigid cyclic MSH core peptides does not participate in binding with the melanocortin receptors.
25 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2019 | 1 |
| 2010 | 2 |
| 2009 | 2 |
| 2006 | 1 |
| 2005 | 1 |
| 2003 | 1 |