title: Effects of the RGTFEGKF inhibitor on the structures of the transmembrane fragment 70-86 of glycophorin A: an all-atom molecular dynamics study.
abstract: There is experimental evidence that the transmembrane fragment spanning amino acids 70-86 of glycophorin A, GpA70-86, forms amyloid fibrils and the inhibitor RGTFEGKF prevents GpA70-86 fibril formation at an equimolar ratio. Both the GpA70-86 and inhibitor peptides contain a GxxxG motif as found in many amyloid proteins such as the Alzheimer's amyloid beta-peptide and prion protein. To explore the intrinsic, early interaction and inhibition mechanism, we have determined the structures of GpA70-86 in the absence and presence of the inhibitor by means of extensive molecular dynamics simulations in explicit solvent. Consistent with experiments on the fibrils, our simulations show that the two GxxxG motifs interact significantly at the monomer level. They go, however, one step beyond by indicating that the inhibitor has a significant impact on the global structure of GpA70-86, but a limited influence on the conformations of the GxxxG motif. Implications of our simulations on amyloid propagation of proteins containing GxxxG motifs are discussed.
authors.affiliation: Surface Physics Laboratory (National Key Laboratory) and Department of Physics, Fudan University, 220 Handan Road, Shanghai, 200433, People's Republic of China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Li
authors.forename: Yin
authors.initials: Y
authors.lastname: Luo
authors.forename: Philippe
authors.initials: P
authors.lastname: Derreumaux
authors.forename: Guanghong
authors.initials: G
authors.lastname: Wei
mesh_terms: D020816:Amino Acid Motifs / Q000187:drug effects; D006021:Glycophorins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects*; D055503:Protein Multimerization / Q000187:drug effects*
chemical_list: D006021:Glycophorins; D010455:Peptides