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PDBsum entry 3bxj
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Signaling protein
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PDB id
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3bxj
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References listed in PDB file
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Key reference
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Title
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The c2 domain of syngap is essential for stimulation of the rap gtpase reaction.
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Authors
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V.Pena,
M.Hothorn,
A.Eberth,
N.Kaschau,
A.Parret,
L.Gremer,
F.Bonneau,
M.R.Ahmadian,
K.Scheffzek.
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Ref.
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Embo Rep, 2008,
9,
350-355.
[DOI no: ]
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PubMed id
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Abstract
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The brain-specific synaptic guanosine triphosphatase (GTPase)-activating protein
(SynGAP) is important in synaptic plasticity. It shows dual specificity for the
small guanine nucleotide-binding proteins Rap and Ras. Here, we show that RapGAP
activity of SynGAP requires its C2 domain. In contrast to the isolated GAP
domain, which does not show any detectable RapGAP activity, a fragment
comprising the C2 and GAP domains (C2-GAP) stimulates the intrinsic GTPase
reaction of Rap by approximately 1 x 10(4). The C2-GAP crystal structure,
complemented by modelling and biochemical analyses, favours a concerted movement
of the C2 domain towards the switch II region of Rap to assist in GTPase
stimulation. Our data support a catalytic mechanism similar to that of canonical
RasGAPs and distinct from the canonical RapGAPs. SynGAP presents the first
example, to our knowledge, of a GAP that uses a second domain for catalytic
activity, thus pointing to a new function of C2 domains.
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