Structure of Rab escort protein-1 in complex with Rab geranylgeranyltransferase.
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.
Pylypenko
Olena
O
Department of Biomolecular Mechanisms, Max-Planck-Institute for Medical Research, Jahnstrasse 29, 69120, Heidelberg, Germany.
Rak
Alexey
A
Reents
Reinhard
R
Niculae
Anca
A
Sidorovitch
Vadim
V
Cioaca
Maria Daniela
MD
Bessolitsyna
Ekaterina
E
Thomä
Nicolas H
NH
Waldmann
Herbert
H
Schlichting
Ilme
I
Goody
Roger S
RS
Alexandrov
Kirill
K
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
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