title: Crystal structures of Hsp104 N-terminal domains from Saccharomyces cerevisiae and Candida albicans suggest the mechanism for the function of Hsp104 in dissolving prions.
abstract: Hsp104 is a yeast member of the Hsp100 family which functions as a molecular chaperone to disaggregate misfolded polypeptides. To understand the mechanism by which the Hsp104 N-terminal domain (NTD) interacts with its peptide substrates, crystal structures of the Hsp104 NTDs from Saccharomyces cerevisiae (ScHsp104NTD) and Candida albicans (CaHsp104NTD) have been determined at high resolution. The structures of ScHsp104NTD and CaHsp104NTD reveal that the yeast Hsp104 NTD may utilize a conserved putative peptide-binding groove to interact with misfolded polypeptides. In the crystal structures ScHsp104NTD forms a homodimer, while CaHsp104NTD exists as a monomer. The consecutive residues Gln105, Gln106 and Lys107, and Lys141 around the putative peptide-binding groove mediate the monomer-monomer interactions within the ScHsp104NTD homodimer. Dimer formation by ScHsp104NTD suggests that the Hsp104 NTD may specifically interact with polyQ regions of prion-prone proteins. The data may reveal the mechanism by which Hsp104 NTD functions to suppress and/or dissolve prions.
authors.affiliation: Department of Cell, Developmental and Integrative Biology (CDIB), University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Cell, Developmental and Integrative Biology (CDIB), University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Jingzhi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Weaver
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Lucius
authors.affiliation: Department of Cell, Developmental and Integrative Biology (CDIB), University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Bingdong
authors.initials: B
authors.lastname: Sha
mesh_terms: D000595:Amino Acid Sequence; D002176:Candida albicans / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation; D000072417:Protein Domains; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; C097188:polyglutamine
keywords: Candida albicans; Hsp104; Saccharomyces cerevisiae; amyloidogenic neurodegenerative diseases; crystal structure; peptide-binding groove; prions; yeast