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PDBsum entry 4phh
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Endocytosis,exocytosis
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PDB id
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4phh
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References listed in PDB file
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Key reference
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Title
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Locking gtpases covalently in their functional states.
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Authors
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D.Wiegandt,
S.Vieweg,
F.Hofmann,
D.Koch,
F.Li,
Y.W.Wu,
A.Itzen,
M.P.Müller,
R.S.Goody.
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Ref.
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Nat Commun, 2015,
6,
7773.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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GTPases act as key regulators of many cellular processes by switching between
active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding
their mode of action has been aided by artificially stabilizing one of these
states either by designing mutant proteins or by complexation with
non-hydrolysable GTP analogues. Because of inherent disadvantages in these
approaches, we have developed acryl-bearing GTP and GDP derivatives that can be
covalently linked with strategically placed cysteines within the GTPase of
interest. Binding studies with GTPase-interacting proteins and X-ray
crystallography analysis demonstrate that the molecular properties of the
covalent GTPase-acryl-nucleotide adducts are a faithful reflection of those of
the corresponding native states and are advantageously permanently locked in a
defined nucleotide (that is active or inactive) state. In a first application,
in vivo experiments using covalently locked Rab5 variants provide new insights
into the mechanism of correct intracellular localization of Rab proteins.
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