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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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Contents |
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* Residue conservation analysis
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PDB id:
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Signaling protein
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Title:
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Crystal structure of the c2-gap fragment of syngap
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Structure:
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Ras gtpase-activating protein syngap. Chain: a, b. Synonym: synaptic ras gtpase-activating protein 1, synaptic ras-gap 1, neuronal rasgap, p135 syngap. Engineered: yes
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Source:
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Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: syngap1. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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3.00Å
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R-factor:
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0.246
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R-free:
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0.289
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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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Key ref:
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V.Pena
et al.
(2008).
The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction.
Embo Rep,
9,
350-355.
PubMed id:
DOI:
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Date:
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14-Jan-08
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Release date:
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25-Mar-08
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PROCHECK
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Headers
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References
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Q9QUH6
(SYGP1_RAT) -
Ras/Rap GTPase-activating protein SynGAP from Rattus norvegicus
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Seq:
Struc:
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1308 a.a.
348 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 24 residue positions (black
crosses)
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DOI no:
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Embo Rep
9:350-355
(2008)
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PubMed id:
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The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.Sot,
C.Kötting,
D.Deaconescu,
Y.Suveyzdis,
K.Gerwert,
and
A.Wittinghofer
(2010).
Unravelling the mechanism of dual-specificity GAPs.
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EMBO J,
29,
1205-1214.
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M.Muhia,
B.K.Yee,
J.Feldon,
F.Markopoulos,
and
I.Knuesel
(2010).
Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.
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Eur J Neurosci,
31,
529-543.
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R.Lam,
V.Romanov,
K.Johns,
K.P.Battaile,
J.Wu-Brown,
J.L.Guthrie,
R.P.Hausinger,
E.F.Pai,
and
N.Y.Chirgadze
(2010).
Crystal structure of a truncated urease accessory protein UreF from Helicobacter pylori.
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Proteins,
78,
2839-2848.
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PDB code:
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X.Ye,
and
T.J.Carew
(2010).
Small G protein signaling in neuronal plasticity and memory formation: the specific role of ras family proteins.
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Neuron,
68,
340-361.
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F.F.Hamdan,
J.Gauthier,
D.Spiegelman,
A.Noreau,
Y.Yang,
S.Pellerin,
S.Dobrzeniecka,
M.Côté,
E.Perreau-Linck,
E.Perreault-Linck,
L.Carmant,
G.D'Anjou,
E.Fombonne,
A.M.Addington,
J.L.Rapoport,
L.E.Delisi,
M.O.Krebs,
F.Mouaffak,
R.Joober,
L.Mottron,
P.Drapeau,
C.Marineau,
R.G.Lafrenière,
J.C.Lacaille,
G.A.Rouleau,
and
J.L.Michaud
(2009).
Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.
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N Engl J Med,
360,
599-605.
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H.He,
T.Yang,
J.R.Terman,
and
X.Zhang
(2009).
Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration.
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Proc Natl Acad Sci U S A,
106,
15610-15615.
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PDB code:
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J.H.Raaijmakers,
and
J.L.Bos
(2009).
Specificity in ras and rap signaling.
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J Biol Chem,
284,
10995-10999.
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O.Neumüller,
M.Hoffmeister,
J.Babica,
C.Prelle,
K.Gegenbauer,
and
A.P.Smolenski
(2009).
Synaptotagmin-like protein 1 interacts with the GTPase-activating protein Rap1GAP2 and regulates dense granule secretion in platelets.
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Blood,
114,
1396-1404.
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S.Kupzig,
D.Bouyoucef-Cherchalli,
S.Yarwood,
R.Sessions,
and
P.J.Cullen
(2009).
The ability of GAP1IP4BP to function as a Rap1 GTPase-activating protein (GAP) requires its Ras GAP-related domain and an arginine finger rather than an asparagine thumb.
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Mol Cell Biol,
29,
3929-3940.
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S.Vilá de Muga,
P.Timpson,
L.Cubells,
R.Evans,
T.E.Hayes,
C.Rentero,
A.Hegemann,
M.Reverter,
J.Leschner,
A.Pol,
F.Tebar,
R.J.Daly,
C.Enrich,
and
T.Grewal
(2009).
Annexin A6 inhibits Ras signalling in breast cancer cells.
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Oncogene,
28,
363-377.
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V.B.Kurella,
J.M.Richard,
C.L.Parke,
L.F.Lecour,
H.D.Bellamy,
and
D.K.Worthylake
(2009).
Crystal Structure of the GTPase-activating Protein-related Domain from IQGAP1.
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J Biol Chem,
284,
14857-14865.
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PDB code:
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Y.Tong,
P.K.Hota,
J.Y.Penachioni,
M.B.Hamaneh,
S.Kim,
R.S.Alviani,
L.Shen,
H.He,
W.Tempel,
L.Tamagnone,
H.W.Park,
and
M.Buck
(2009).
Structure and function of the intracellular region of the plexin-b1 transmembrane receptor.
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J Biol Chem,
284,
35962-35972.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
