1plw
From Proteopedia
NMR structure of Methionine-Enkephalin in fast tumbling DMPC/DHPC bicelles
Structural highlights
FunctionPENK_HUMAN Met- and Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress. PENK(114-133) and PENK(237-258) increase glutamate release in the striatum. PENK(114-133) decreases GABA concentration in the striatum. Publication Abstract from PubMedEnkephalins are pentapeptides found in the central nervous system. It is believed that these neuropeptides interact with the nerve cell membrane to adopt a conformation suitable for their binding to an opiate receptor. In this work, we have determined the three-dimensional structure of methionine-enkephalin (Menk) in fast-tumbling bicelles using multidimensional (1)H NMR. Bicelles were selected as model membranes because both their bilayer organization and composition resemble those of natural biomembranes. The effect of the membrane composition on the peptide conformation was explored using both zwitterionic (PC bicelles) and negatively charged bicelles (Bic/PG). Pulsed field gradient experiments allowed the determination of the proportion of Menk bound to the model membranes. Approximately 60% of the water-soluble enkephalin was found to associate to the bicellar systems. Structure calculations from torsion angle and NOE-based distance constraints suggest the presence of both micro - and delta-selective conformers of Menk in each system and slightly different conformers in PC bicelles and Bic/PG. As opposed to previous studies of enkephalins in membrane mimetic systems, our results show that these opiate peptides could adopt several conformations in a membrane environment, which is consistent with the flexibility and poor selectivity of enkephalins. A multidimensional 1H NMR investigation of the conformation of methionine-enkephalin in fast-tumbling bicelles.,Marcotte I, Separovic F, Auger M, Gagne SM Biophys J. 2004 Mar;86(3):1587-600. PMID:14990485[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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