Solution structure of humanin, a peptide against Alzheimer's disease-related neurotoxicity.
Humanin is a newly identified 24-residue peptide that suppresses neuronal cell death caused by a wide spectrum of familial Alzheimer's disease genes and the beta-amyloid peptide. In this study, NMR and circular dichroism studies of synthetic humanin in aqueous and 30% 2,2,2-trifluoroethanol (TFE) solutions are reported. In aqueous solution, humanin exists predominantly in an unstructured conformation in equilibrium with turn-like structures involving residues Gly5 to Leu10 and Glu15 to Leu18, providing indication of nascent helix. In the less polar environment of 30% TFE, humanin readily adopts helical structure with long-range order spanning residues Gly5 to Leu18. Comparative 3D modeling studies and topology predictions are in qualitative agreement with the experimental findings in both environments. Our studies reveal a flexible peptide in aqueous environment, which is free to interact with possible receptors that mediate its action, but may also acquire a helical conformation necessary for specific interactions and/or passage through membranes.
Benaki
Dimitra
D
Institute of Biology, NCSR Demokritos, 153 10 Athens, Greece.
Zikos
Christos
C
Evangelou
Alexandra
A
Livaniou
Evangelia
E
Vlassi
Metaxia
M
Mikros
Emmanuel
E
Pelecanou
Maria
M
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D013696:Temperature; D014270:Trifluoroethanol / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; C427211:humanin; D014867:Water; D018698:Glutamic Acid; D014270:Trifluoroethanol; D007930:Leucine; D005998:Glycine