Solution structure of Ser14Gly-humanin, a potent rescue factor against neuronal cell death in Alzheimer's disease.
The NMR solution study of Ser14Gly-humanin (S14G-HN), a 1000-fold more potent derivative of humanin (HN), is reported. HN is 24-residue peptide that selectively suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults and offers hope for the development of a cure against AD. In aqueous solution the NMR data show that S14G-HN is a flexible peptide with turn-like structures in its conformational ensemble distributed over an extensive part of its sequence from Pro3 to Glu15. In the more lipophilic environment of 30% TFE, an alpha-helical structure spanning residues Phe6 to Thr13 is identified. Comparison of these findings to the NMR structure of the parent HN and to existing structure-function relationship literature data outlines the important for activity structural features for this class of neuroprotective peptides, and brings forth flexibility as an important characteristic that may facilitate interactions with functional counterparts of the neuroprotection pathway.
Benaki
Dimitra
D
Institute of Biology, NCSR Demokritos 15310 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*; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D002942:Circular Dichroism; D005998:Glycine / Q000737:chemistry*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012694:Serine / Q000737:chemistry*
D047908:Intracellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; C427211:humanin; D012694:Serine; D005998:Glycine