title: The Chaperone Activity of the Developmental Small Heat Shock Protein Sip1 Is Regulated by pH-Dependent Conformational Changes.
abstract: Small heat shock proteins (sHsps) are ubiquitous molecular chaperones that prevent the aggregation of unfolding proteins during proteotoxic stress. In Caenorhabditis elegans, Sip1 is the only sHsp exclusively expressed in oocytes and embryos. Here, we demonstrate that Sip1 is essential for heat shock survival of reproducing adults and embryos. X-ray crystallography and electron microscopy revealed that Sip1 exists in a range of well-defined globular assemblies consisting of two half-spheres, each made of dimeric "spokes." Strikingly, the oligomeric distribution of Sip1 as well as its chaperone activity depend on pH, with a trend toward smaller species and higher activity at acidic conditions such as present in nematode eggs. The analysis of the interactome shows that Sip1 has a specific substrate spectrum including proteins that are essential for embryo development.
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Tilly
authors.initials: T
authors.lastname: Fleckenstein
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kastenmüller
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Martin Lorenz
authors.initials: ML
authors.lastname: Stein
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Peters
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Daake
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Krause
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Weinfurtner
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Haslbeck
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany. Electronic address: sevil.weinkauf@tum.de.
authors.forename: Sevil
authors.initials: S
authors.lastname: Weinkauf
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany. Electronic address: michael.groll@mytum.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.affiliation: Center for Integrated Protein Science, Fakultät für Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748 Garching, Germany. Electronic address: johannes.buchner@tum.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D050888:Heat-Shock Proteins, Small / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013696:Temperature
chemical_list: D029742:Caenorhabditis elegans Proteins; D050888:Heat-Shock Proteins, Small; D018832:Molecular Chaperones; C102603:sip-1 protein, C elegans