3bxj
From Proteopedia
Crystal Structure of the C2-GAP Fragment of synGAP
Structural highlights
Function[SYGP1_RAT] Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction.,Pena V, Hothorn M, Eberth A, Kaschau N, Parret A, Gremer L, Bonneau F, Ahmadian MR, Scheffzek K EMBO Rep. 2008 Apr;9(4):350-5. Epub 2008 Mar 7. PMID:18323856[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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