title: Recognition of a functional peroxisome type 1 target by the dynamic import receptor pex5p.
abstract: Peroxisomes require the translocation of folded and functional target proteins of various sizes across the peroxisomal membrane. We have investigated the structure and function of the principal import receptor Pex5p, which recognizes targets bearing a C-terminal peroxisomal targeting signal type 1. Crystal structures of the receptor in the presence and absence of a peroxisomal target, sterol carrier protein 2, reveal major structural changes from an open, snail-like conformation into a closed, circular conformation. These changes are caused by a long loop C terminal to the 7-fold tetratricopeptide repeat segments. Mutations in residues of this loop lead to defects in peroxisomal import in human fibroblasts. The structure of the receptor/cargo complex demonstrates that the primary receptor-binding site of the cargo is structurally and topologically autonomous, enabling the cargo to retain its native structure and function.
authors.affiliation: European Molecular Biology Laboratory-Hamburg Outstation, Notkestrasse 85, 22603 Hamburg.
authors.forename: Will A
authors.initials: WA
authors.lastname: Stanley
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory-Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg.
authors.forename: Fabian V
authors.initials: FV
authors.lastname: Filipp
authors.affiliation: European Molecular Biology Laboratory-Hamburg Outstation, Notkestrasse 85, 22603 Hamburg.
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
authors.affiliation: European Molecular Biology Laboratory-Hamburg Outstation, Notkestrasse 85, 22603 Hamburg.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schüller
authors.affiliation: Department of Systems Biology, Institute for Physiological Chemistry, Faculty of Medicine, Ruhr University of Bochum, 44780 Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Erdmann
authors.affiliation: Department of Systems Biology, Institute for Physiological Chemistry, Faculty of Medicine, Ruhr University of Bochum, 44780 Bochum, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schliebs
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory-Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg.
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.affiliation: European Molecular Biology Laboratory-Hamburg Outstation, Notkestrasse 85, 22603 Hamburg. Electronic address: wilmanns@embl-hamburg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wilmanns
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*
chemical_list: D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear