title: Structure analysis of the protein transduction domain of human Period1 and its mutant analogs.
abstract: Human Period1 (hPer1) has been proved to be able to translocate into cells in a protein transduction manner. The segment of amino acids 830-845 of hPer1 is its protein transduction domain (PTD). In order to explore the membrane penetrating mechanism of hPer1-PTD and the physico-chemical properties necessary in the process, Ala scanning mutation method was used to investigate the variation in the peptide internalization. To further investigate the related physico-chemical requirements, the three dimensional structures of hPer1-PTD and its mutant analogs were simulated by Rosetta method. The electrostatic potentials and energies of these structures were calculated using the Delphi algorithm to solve Poisson-Boltzman equation. The hydrophobicity was assessed by the percentage of the nonpolar area in SAS (solvent accessible surface (SAS)). It has been proved that the Arg836 was the key residue for peptide internalization. When this Arg mutated into Ala, the peptide could not cross the membrane. The large enough area with positive charge was the decisive factor for hPer1-PTD. The alpha-helical structure seemed to play an assistant role so as to enable the positive charge connected in spatial arrangement.
authors.affiliation: Department of Biomedical Engineering, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Xiao Lin
authors.initials: XL
authors.lastname: Yang
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Bo
authors.initials: B
authors.lastname: Niu
authors.forename: Xiao Nian
authors.initials: XN
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiang
authors.forename: Yue Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Zheng Guo
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D016466:CHO Cells; D018797:Cell Cycle Proteins; D006224:Cricetinae; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D056950:Period Circadian Proteins; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; D056950:Period Circadian Proteins; D011994:Recombinant Proteins; D001120:Arginine