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PDBsum entry 3tw8
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Protein transport
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PDB id
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3tw8
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Contents |
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343 a.a.
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169 a.a.
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362 a.a.
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References listed in PDB file
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Key reference
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Title
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Insights regarding guanine nucleotide exchange from the structure of a denn-Domain protein complexed with its rab gtpase substrate.
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Authors
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X.Wu,
M.J.Bradley,
Y.Cai,
D.Kümmel,
E.M.De la cruz,
F.A.Barr,
K.M.Reinisch.
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Ref.
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Proc Natl Acad Sci U S A, 2011,
108,
18672-18677.
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PubMed id
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Abstract
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Rab GTPases are key regulators of membrane traffic pathways within eukaryotic
cells. They are specifically activated by guanine nucleotide exchange factors
(GEFs), which convert them from their "inactive" GDP-bound form to the
"active" GTP-bound form. In higher eukaryotes, proteins containing
DENN-domains comprise a major GEF family. Here we describe at 2.1-Å resolution
the first structure of a DENN-domain protein, DENND1B-S, complexed with its
substrate Rab35, providing novel insights as to how DENN-domain GEFs interact
with and activate Rabs. DENND1B-S is bi-lobed, and interactions with Rab35 are
through conserved surfaces in both lobes. Rab35 binds via switch regions I and
II, around the nucleotide-binding pocket. Positional shifts in Rab residues
required for nucleotide binding may lower its affinity for bound GDP, and a
conformational change in switch I, which makes the nucleotide-binding pocket
more solvent accessible, likely also facilitates exchange.
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