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PDBsum entry 1l4a
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Endocytosis/exocytosis
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PDB id
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1l4a
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Contents |
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66 a.a.
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82 a.a.
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73 a.a.
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75 a.a.
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28 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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X-Ray structure of a neuronal complexin-Snare complex from squid.
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Authors
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A.Bracher,
J.Kadlec,
H.Betz,
W.Weissenhorn.
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Ref.
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J Biol Chem, 2002,
277,
26517-26523.
[DOI no: ]
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PubMed id
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Abstract
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Nerve terminals release neurotransmitters from vesicles into the synaptic cleft
upon transient increases in intracellular Ca(2+). This exocytotic process
requires the formation of trans SNARE complexes and is regulated by accessory
proteins including the complexins. Here we report the crystal structure of a
squid core complexin-SNARE complex at 2.95-A resolution. A helical segment of
complexin binds in anti-parallel fashion to the four-helix bundle of the core
SNARE complex and interacts at its C terminus with syntaxin and synaptobrevin
around the ionic zero layer of the SNARE complex. We propose that this structure
is part of a multiprotein fusion machinery that regulates vesicle fusion at a
late pre-fusion stage. Accordingly, Ca(2+) may initiate membrane fusion by
acting directly or indirectly on complexin, thus allowing the conformational
transitions of the trans SNARE complex that are thought to drive membrane fusion.
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Figure 2.
Fig. 2. a, alignment of squid SNARE sequences from Sb ,
Sx, Sn1, and Sn2, present in the crystal structure, and their
respective rat SNARE complex sequences. The positions of heptad
repeat layers are indicated based on the rat SNARE complex
structure (7) and our squid SNARE complex structure. The
residues contacting cpx are marked with asterisks. Sequence
identities between rat and squid chains are 91% for Sb, 87% for
Sx, 79% for Sn1, and 68% for Sn2 considering only the SNARE
motifs (layers  7 to +8).
Hydrophobic layers are highlighted in gray, and the numbering is
according to the squid sequences. b, sequence alignment of rat
cpx I and II and squid cpx. The residues present in the
structure are shown, and the construct used in crystallization
is indicated as dashed lines. Residues contacting Sx and Sb are
marked with asterisks. Identical residues are highlighted in
black boxes, and similar residues are shaded in gray. The
numbering is according to the squid sequence.
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Figure 3.
Fig. 3. cpx interacts with the SNARE protein chains Sb
and Sx between layers 3 and +1.
Close-up views of the three major cross sections of
cpx·SNARE complex interactions. For clarity, only
hydrophobic layer residues and contact residues are shown. Polar
interactions are indicated as dashed lines. a, cross-section of
hydrophilic and hydrophobic interactions at layer 3.
Complexin Tyr-73 packs anti-clockwise against Sx Met-218 and Sb
Arg-56 following the classical "knobs into holes" arrangement.
b, cross-section of predominately hydrophobic interactions at
layer 1. Note
that the cpx helix is closer to the Sb helix than to the Sx
helix, and the packing deviates from the "knobs into holes"
arrangement. c, cross-section of interactions at the ionic 0
layer, which are mostly hydrophilic. The hydrogen bond distances
are indicated for the SNARE residues.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
26517-26523)
copyright 2002.
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