NMR studies of the structure and dynamics of peptide E, an endogenous opioid peptide that binds with high affinity to multiple opioid receptor subtypes

Yan, Chunhua; DiGate, Russell J.; Guiles, R. D.

doi:10.1002/(sici)1097-0282(199901)49:1<55::aid-bip6>3.0.co;2-a

Cited by 15 publications

(26 citation statements)

References 54 publications

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“…Differential PE processing results in a diversity of posttranslational products and potential modes of action on OLs. Products of the gene that are κ‐agonists could be responsible for some protective effects, since smaller PE derivatives are typically secreted and activate cell surface κ‐receptors with high affinity (Benyhe et al, 1997; Davis et al, 1990; Stevens et al, 1998; Yan et al, 1999). As described in other cells, intact or partially processed PE might also traffic into the nucleus to function in transcriptional regulation (Bakalkin et al, 1991; Bottger and Spruce, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…These include dynorphin A and many of its metabolites derived from prodynorphin (Chavkin et al, 1982; James et al, 1984). They also include peptides derived from proenkephalin: peptide E (Quirion and Weiss, 1983; Yan et al, 1999), BAM‐22 (Quirion and Weiss, 1983), BAM‐18 (Stevens et al, 1998), BAM‐12 (Davis et al, 1990; Quirion and Weiss, 1983), [Met 5 ] enkephalin‐Arg 6 ‐Gly 7 ‐Leu 8 (MERGL) (Schulz et al, 1982), and [Met 5 ]‐enkephalin‐Arg 6 ‐Phe 7 (MERF) (Benyhe et al, 1997). Proenkephalin (PE) is especially interesting because of the diversity of its posttranslational products and potential modes of action.…”

Section: Introductionmentioning

confidence: 99%

“…For example, PE encoding sequences in DNA are directly targeted by the YY1 transcription factor (Bakalkin et al, 1995, 1997). Alternatively, intact or partially processed PE can traffic into the nucleus and may itself act as a transcriptional regulator (Bakalkin et al, 1991; Bottger and Spruce, 1995), while smaller PE derivatives are typically secreted and can activate δ‐ or κ‐receptors at the cell surface with high affinity (Benyhe et al, 1997; Davis et al, 1990; Stevens et al, 1998; Yan et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Vesicle-associated membrane protein isoforms in the tiger salamander retina

2001

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Vesicle associated membrane protein (VAMP; also known as synaptobrevin) is a key component of the core complex needed for docking and fusion of synaptic vesicles with the presynaptic plasma membrane. Recent work indicates that the precise complement of presynaptic proteins associated with transmitter release and their isoforms vary among synapses, presumably conferring specific functional release properties. The retina contains two types of vesicular synapses with distinct morphologic, functional, and biochemical characteristics: ribbon and conventional synapses. Although the precise complement of presynaptic proteins is known to differ between conventional and ribbon synapses and among conventional synapses, the distribution of VAMP isoforms among retinal synapses has not been determined. The expression and localization of VAMP isoforms in the salamander retina, a major model system for studies of retinal circuitry, was examined by using immunocytochemical and immunoblotting methods. Both methods indicated that at least two VAMP isoforms were expressed in salamander retina. One isoform, recognized by an immunoglobulin M antibody that recognizes both mammalian VAMP-1 and VAMP-2, was associated with photoreceptor and bipolar cell terminals as well as many conventional synapses, and probably corresponds to mammalian VAMP-2. A different VAMP isoform associated with a subset of amacrine cells, was recognized only by antibodies directed against the N-terminus of mammalian VAMP-2. An antiserum directed against the N-terminus of mammalian VAMP-1 did not specifically recognize any salamander VAMPs in either immunocytochemical or immunoblotting experiments. Heterogeneous distribution of VAMP isoforms among conventional retinal synapses was confirmed by double labeling for synapsin I, a marker for conventional synapses. These studies indicate that VAMP isoforms are expressed heterogeneously among retinal synapses but cannot account for the differences in transmitter release characteristics at ribbon and conventional synapses. These results also corroborate previous studies in Xenopus indicating that the N-terminus of nonmammalian VAMP isoforms differs from their mammalian counterparts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vesicle-associated membrane protein isoforms in the tiger salamander retina

2001

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“…Opioid peptides have often been studied in media similar to the membrane environment, usually aqueous micellar solutions. The micelles generally used are based on SDS, a detergent easy to find in perdeuterated form [26][27][28][29], but there are also published studies of micelles of phospholipids [30][31][32][33][34][35][36].…”

Section: Membranesmentioning

confidence: 99%

Solution structure of nociceptin peptides

Amodeo

Guerrini

Picone

et al. 2002

Journal of Peptide Science

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Peptides embedded in the sequence of pre-pro-nociceptin, i.e. nociceptin, nocistatin and orphanin FQ2, have shed light on the complexity of the mechanisms involving the peptide hormones related to pain and have opened up new perspectives for the clinical treatment of pain. The design of new ligands with high selectivity and bioavailability, in particular for ORL1, is important both for the elucidation and control of the physiological role of the receptor and for their therapeutic importance. The failure to obtain agonists and antagonists when using, for nociceptin, the same substitutions that are successful for opioids, and the conformational flexibility of them all, justify systematic efforts to study the solution conformation under conditions as close as possible to their natural environment. Structural studies of linear peptides in solution are hampered by their high flexibility. A direct structural study of the complex between a peptide and its receptor would overcome this difficulty, but such a study is not easy since opioid receptors are membrane proteins. Thus, conformational studies of lead peptides in solution are still important for drug design. This review deals with conformational studies of natural pre-nociceptin peptides in several solvents that mimic in part the different environments in which the peptides exert their action. None of the structural investigations yielded a completely reliable bioactive conformation, but the global conformation of the peptides in biomimetic environments can shed light on their interaction with receptors.

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“…The peptide dynorphin A is an endogenous ligand selective for the -opioid receptor (Chavkin et al, 1982;Chavkin and Goldstein, 1981), and its potential as an analgesic has made it an attractive target for research since its discovery more than two decades ago (Cox et al, 1975). The structures of opioid ligands such as dynorphin have been studied with spectroscopic methods in various solvents (Saviano et al, 1999;Segawa et al, 1995;Yan et al, 1999;Tessmer and Kallick, 1997). The naturally occurring Dynorphin A has 17 amino acids with the sequence H-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln-OH (Goldstein et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics Simulations Predict a Tilted Orientation for the Helical Region of Dynorphin A(1–17) in Dimyristoylphosphatidylcholine Bilayers

Sankararamakrishnan

Weinstein

2000

Biophysical Journal

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The structural properties of the endogenous opioid peptide dynorphin A(1-17) (DynA), a potential analgesic, were studied with molecular dynamics simulations in dimyristoylphosphatidylcholine bilayers. Starting with the known NMR structure of the peptide in dodecylphosphocholine micelles, the N-terminal helical segment of DynA (encompassing residues 1-10) was initially inserted in the bilayer in a perpendicular orientation with respect to the membrane plane. Parallel simulations were carried out from two starting structures, systems A and B, that differ by 4 A in the vertical positioning of the peptide helix. The complex consisted of approximately 26,400 atoms (dynorphin + 86 lipids + approximately 5300 waters). After >2 ns of simulation, which included >1 ns of equilibration, the orientation of the helical segment of DynA had undergone a transition from parallel to tilted with respect to the bilayer normal in both the A and B systems. When the helix axis achieved a approximately 50 degrees angle with the bilayer normal, it remained stable for the next 1 ns of simulation. The two simulations with different starting points converged to the same final structure, with the helix inserted in the bilayer throughout the simulations. Analysis shows that the tilted orientation adopted by the N-terminal helix is due to specific interactions of residues in the DynA sequence with phospholipid headgroups, water, and the hydrocarbon chains. Key elements are the "snorkel model"-type interactions of arginine side chains, the stabilization of the N-terminal hydrophobic sequence in the lipid environment, and the specific interactions of the first residue, Tyr. Water penetration within the bilayer is facilitated by the immersed DynA, but it is not uniform around the surface of the helix. Many water molecules surround the arginine side chains, while water penetration near the helical surface formed by hydrophobic residues is negligible. A mechanism of receptor interaction is proposed for DynA, involving the tilted orientation observed from these simulations of the peptide in the lipid bilayer.

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NMR studies of the structure and dynamics of peptide E, an endogenous opioid peptide that binds with high affinity to multiple opioid receptor subtypes

Cited by 15 publications

References 54 publications

Vesicle-associated membrane protein isoforms in the tiger salamander retina

Vesicle-associated membrane protein isoforms in the tiger salamander retina

Solution structure of nociceptin peptides

Molecular Dynamics Simulations Predict a Tilted Orientation for the Helical Region of Dynorphin A(1–17) in Dimyristoylphosphatidylcholine Bilayers

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