Structure changes of natively disordered Humanin in the presence of lipid.
While neuroprotective activities of Humanin peptides have been clearly demonstrated, the functional mechanism has not been fully understood. Humanin and a majority of Humanin analogs showed a disordered structure at low peptide concentrations and aggregation at higher concentrations in aqueous solution at pH 7.0. Here we have examined the structure in lipid environments, i.e., in the presence of liposome by circular dichroism. Humanin underwent a large structure change into a typical beta-sheet structure at neutral pH in the presence liposome made of a negatively charged 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG), but not an electrically neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC). As Humanin possesses a positive charge at neutral pH, the observed structure changes with DOPG suggest electrostatic binding of the peptide with the lipid. No effect of NaCl on the Humanin structure was observed in neutral solution and in the presence of DOPC liposome. Increasing temperature resulted in changes in the structure due to aggregation. On the other hand, the effects of temperature on the Humanin structure showed that it has a relatively stable structure in the presence of DOPG liposome independent of the presence of NaCl.
Hirano
Atsushi
A
Institute of Applied Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
Shiraki
Kentaro
K
Niikura
Takako
T
Arakawa
Tsutomu
T
Kita
Yoshiko
Y
D000595:Amino Acid Sequence; D002021:Buffers; D002942:Circular Dichroism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000494:pharmacology*; D010715:Phosphatidylglycerols / Q000494:pharmacology*; D020836:Protein Structure, Quaternary; D012996:Solutions; D013696:Temperature; D013997:Time Factors
D002021:Buffers; D047908:Intracellular Signaling Peptides and Proteins; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D012996:Solutions; C427211:humanin; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; C017251:1,2-oleoylphosphatidylcholine