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PDBsum entry 3dss
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References listed in PDB file
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Key reference
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Title
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Structures of rabggtase-Substrate/product complexes provide insights into the evolution of protein prenylation.
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Authors
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Z.Guo,
Y.W.Wu,
D.Das,
C.Delon,
J.Cramer,
S.Yu,
S.Thuns,
N.Lupilova,
H.Waldmann,
L.Brunsveld,
R.S.Goody,
K.Alexandrov,
W.Blankenfeldt.
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Ref.
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Embo J, 2008,
27,
2444-2456.
[DOI no: ]
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PubMed id
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Abstract
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Post-translational isoprenylation of proteins is carried out by three related
enzymes: farnesyltransferase, geranylgeranyl transferase-I, and Rab
geranylgeranyl transferase (RabGGTase). Despite the fact that the last one is
responsible for the largest number of individual protein prenylation events in
the cell, no structural information is available on its interaction with
substrates and products. Here, we present structural and biophysical analyses of
RabGGTase in complex with phosphoisoprenoids as well as with the prenylated
peptides that mimic the C terminus of Rab7 GTPase. The data demonstrate that,
unlike other protein prenyl transferases, both RabGGTase and its substrate
RabGTPases completely 'outsource' their specificity for each other to an
accessory subunit, the Rab escort protein (REP). REP mediates the placement of
the C terminus of RabGTPase into the active site of RabGGTase through a series
protein-protein interactions of decreasing strength and selectivity. This
arrangement enables RabGGTase to prenylate any cysteine-containing sequence. On
the basis of our structural and thermodynamic data, we propose that RabGGTase
has evolved from a GGTase-I-like molecule that 'learned' to interact with a
recycling factor (GDI) that, in turn, eventually gave rise to REP.
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