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PDBsum entry 1dce
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of rab geranylgeranyltransferase at 2.0 a resolution.
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Authors
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H.Zhang,
M.C.Seabra,
J.Deisenhofer.
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Ref.
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Structure, 2000,
8,
241-251.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Rab geranylgeranyltransferase (RabGGT) catalyzes the addition of two
geranylgeranyl groups to the C-terminal cysteine residues of Rab proteins, which
is crucial for membrane association and function of these proteins in
intracellular vesicular trafficking. Unlike protein farnesyltransferase (FT) and
type I geranylgeranyltransferase, which both prenylate monomeric small G
proteins or short peptides, RabGGT can prenylate Rab only when Rab is in a
complex with Rab escort protein (REP). RESULTS: The crystal structure of rat
RabGGT at 2.0 A resolution reveals an assembly of four distinct structural
modules. The beta subunit forms an alpha-alpha barrel that contains most of the
residues in the active site. The alpha subunit consists of a helical domain, an
immunoglobulin (Ig)-like domain, and a leucine-rich repeat (LRR) domain. The
N-terminal region of the alpha subunit binds to the active site in the beta
subunit; residue His2alpha directly coordinates a zinc ion. The prenyl-binding
pocket of RabGGT is deeper than that in FT. CONCLUSIONS: LRR and Ig domains are
often involved in protein-protein interactions; in RabGGT they might participate
in the recognition and binding of REP. The binding of the N-terminal peptide of
the alpha subunit to the active site suggests an autoinhibition mechanism that
might contribute to the inability of RabGGT to recognize short peptides or Rab
alone as its substrate. Replacement of residues Trp102beta and Tyr154beta in FT
by Ser48beta and Leu99beta, respectively, in RabGGT largely determine the
different lipid-binding specificities of the two enzymes.
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Figure 1.
Figure 1. Ribbon representation of the RabGGT structure
(cyan, helical domain of the a subunit; orange, Ig-like domain;
green, LRR domain; purple, b subunit; blue, 3[10] helices of all
domains). (a) Complete structure of RabGGT. (b) The helical
domain and LRR domain of RabGGTa in a slightly different
orientation from (a). The 15 helices are numbered from a1 to
a15. (c) The Ig-like domain of RabGGTa. The strands are labelled
according to the convention in [34]. (d) The b subunit of
RabGGT, with the zinc ion shown as a red ball and the ligands
Asp238b, Cys240b and His290b in ball-and-stick representation.
The helices are numbered b1-b14.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2000,
8,
241-251)
copyright 2000.
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