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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkyl and Aryl Transferases / chemistry*
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Alkyl and Aryl Transferases / genetics
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Alkyl and Aryl Transferases / metabolism
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Amino Acid Sequence
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Animals
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Binding Sites
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Guanine Nucleotide Dissociation Inhibitors / chemistry
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Guanine Nucleotide Dissociation Inhibitors / genetics
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Guanine Nucleotide Dissociation Inhibitors / metabolism
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In Vitro Techniques
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Lipid Metabolism
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis
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Protein Conformation
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Sequence Homology, Amino Acid
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Signal Transduction
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rab GTP-Binding Proteins / chemistry*
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rab GTP-Binding Proteins / genetics
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rab GTP-Binding Proteins / metabolism
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rab3A GTP-Binding Protein / chemistry
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rab3A GTP-Binding Protein / genetics
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rab3A GTP-Binding Protein / metabolism
Substances
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GDP dissociation inhibitor 1
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Guanine Nucleotide Dissociation Inhibitors
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Macromolecular Substances
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Alkyl and Aryl Transferases
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Rab geranylgeranyltransferase
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rab GTP-Binding Proteins
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rab3A GTP-Binding Protein