title: Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransferase.
abstract: Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP). The crystal structure of isoprenoid-bound RabGGTase complexed to REP-1 has been solved to 2.7 A resolution. The complex interface buries a surprisingly small surface area of ca. 680 A and is unexpectedly formed by helices 8, 10, and 12 of the RabGGTase alpha subunit and helices D and E of REP-1. We demonstrate that the affinity of RabGGTase for REP-1 is allosterically regulated by phosphoisoprenoid via a long-range trans-domain signal transduction event. Comparing the structure of REP-1 with the closely related RabGDI, we conclude that the specificity of the REP:RabGGTase interaction is defined by differently positioned phenylalanine residues conserved in the REP and GDI subfamilies.
authors.affiliation: Department of Biomolecular Mechanisms, Max-Planck-Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany.
authors.forename: Olena
authors.initials: O
authors.lastname: Pylypenko
authors.forename: Alexey
authors.initials: A
authors.lastname: Rak
authors.forename: Reinhard
authors.initials: R
authors.lastname: Reents
authors.forename: Anca
authors.initials: A
authors.lastname: Niculae
authors.forename: Vadim
authors.initials: V
authors.lastname: Sidorovitch
authors.forename: Maria Daniela
authors.initials: MD
authors.lastname: Cioaca
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Bessolitsyna
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Thomä
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: Ilme
authors.initials: I
authors.lastname: Schlichting
authors.forename: Roger S
authors.initials: RS
authors.lastname: Goody
authors.forename: Kirill
authors.initials: K
authors.lastname: Alexandrov
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C086796:GDP dissociation inhibitor 1; D020730:Guanine Nucleotide Dissociation Inhibitors; D046911:Macromolecular Substances; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase; D020691:rab GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein