title: Effects of novel peptides derived from the acidic tail of synuclein (ATS) on the aggregation and stability of fusion proteins.
abstract: The acidic tail of alpha-synuclein (ATSalpha) has been shown to protect the glutathione S-transferase (GST)-ATSalpha fusion protein from environmental stresses, such as heat, pH and metal ions. In this study, we further demonstrated that the introduction of ATSalpha into other proteins, such as dehydrofolate reductase and adiponectin, renders the fusion proteins resistant to heat-induced aggregation and that the acidic tail of beta- or gamma-synuclein can also protect the fusion proteins from heat-induced aggregation. Interestingly, the heat resistance of GST-ATSalpha deletion mutants, which contain shorter peptides derived from the highly charged regions of ATSalpha, was approximately proportional to the number of added Glu/Asp residues. However, the negative charges in the ATSalpha-derived peptides appear insufficient to explain the extreme heat resistance of the fusion proteins, since polyglutamates appeared to be much less effective than the ATSalpha-derived peptides in conferring heat resistance on the fusion proteins. These results suggest that not only the negatively charged residues but also the specific amino acid sequence of ATSalpha play an important role in conferring extreme heat resistance on the fusion proteins. Furthermore, the heat-induced secondary structural changes and thermal inactivation curves of GST-ATSalpha deletion mutants indicated that the introduction of ATSalpha-derived peptides does not significantly affect the intrinsic stability of the fusion proteins.
authors.affiliation: Department of Microbiology and Brain Korea 21 Project of Medical Sciences, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea.
authors.forename: Sang Myun
authors.initials: SM
authors.lastname: Park
authors.forename: Keun Jae
authors.initials: KJ
authors.lastname: Ahn
authors.forename: Han Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Jeon Han
authors.initials: JH
authors.lastname: Park
authors.forename: Jongsun
authors.initials: J
authors.lastname: Kim
mesh_terms: D052242:Adiponectin; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005982:Glutathione Transferase / Q000378:metabolism; D006358:Hot Temperature; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D013056:Spectrophotometry, Ultraviolet; D051843:Synucleins; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D051844:alpha-Synuclein; D051845:gamma-Synuclein
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D051845:gamma-Synuclein; D013762:Tetrahydrofolate Dehydrogenase; D005982:Glutathione Transferase