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PDBsum entry 2zw3
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Cell adhesion
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PDB id
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2zw3
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Contents |
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* Residue conservation analysis
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PDB id:
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Cell adhesion
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Title:
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Structure of the connexin-26 gap junction channel at 3.5 angstrom resolution
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Structure:
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Gap junction beta-2 protein. Chain: a, b, c, d, e, f. Synonym: connexin-26, cx26. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
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Resolution:
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3.50Å
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R-factor:
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0.338
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R-free:
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0.351
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Authors:
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S.Maeda,S.Nakagawa,M.Suga,E.Yamashita,A.Oshima,Y.Fujiyoshi, T.Tsukihara
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Key ref:
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S.Maeda
et al.
(2009).
Structure of the connexin 26 gap junction channel at 3.5 A resolution.
Nature,
458,
597-602.
PubMed id:
DOI:
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Date:
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01-Dec-08
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Release date:
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07-Apr-09
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PROCHECK
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Headers
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References
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P29033
(CXB2_HUMAN) -
Gap junction beta-2 protein from Homo sapiens
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Seq:
Struc:
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226 a.a.
201 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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DOI no:
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Nature
458:597-602
(2009)
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PubMed id:
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Structure of the connexin 26 gap junction channel at 3.5 A resolution.
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S.Maeda,
S.Nakagawa,
M.Suga,
E.Yamashita,
A.Oshima,
Y.Fujiyoshi,
T.Tsukihara.
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ABSTRACT
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Gap junctions consist of arrays of intercellular channels between adjacent cells
that permit the exchange of ions and small molecules. Here we report the crystal
structure of the gap junction channel formed by human connexin 26 (Cx26, also
known as GJB2) at 3.5 A resolution, and discuss structural determinants of
solute transport through the channel. The density map showed the two
membrane-spanning hemichannels and the arrangement of the four transmembrane
helices of the six protomers forming each hemichannel. The hemichannels feature
a positively charged cytoplasmic entrance, a funnel, a negatively charged
transmembrane pathway, and an extracellular cavity. The pore is narrowed at the
funnel, which is formed by the six amino-terminal helices lining the wall of the
channel, which thus determines the molecular size restriction at the channel
entrance. The structure of the Cx26 gap junction channel also has implications
for the gating of the channel by the transjunctional voltage.
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Selected figure(s)
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Figure 2.
Figure 2: Stereo view of the Cx26 protomer in ribbon
representation. Colour code: red, NTH; blue, TM1–TM4;
green, E1; yellow, E2; grey, disulphide bonds; dashed lines,
cytoplasmic loop (CL) and C terminus (CT), which were not
visible in the map. E1 and E2 are the loops connecting TM1 and
TM2, and TM3 and TM4, respectively.
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Figure 5.
Figure 5: Structure of the pore funnel. The six NTHs form a
funnel structure, which is stabilized by a circular network of
hydrogen bonds between Asp 2 and the main chain of Thr 5. The
Cx26 protomers are shown in line and the NTHs in ribbon
representation superposed on a surface representation. The
close-up view shows the interaction between the indole ring of
Trp 3 and the methyl group of Met 34 (TM1) in the adjacent
protomer (hydrophobic interaction: orange broken line; hydrogen
bond: red broken line).
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2009,
458,
597-602)
copyright 2009.
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Figures were
selected
by an automated process.
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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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A.D.Martínez,
J.Maripillán,
R.Acuña,
P.J.Minogue,
V.M.Berthoud,
and
E.C.Beyer
(2011).
Different domains are critical for oligomerization compatibility of different connexins.
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Biochem J,
436,
35-43.
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C.Sotelo
(2011).
Camillo Golgi and Santiago Ramon y Cajal: the anatomical organization of the cortex of the cerebellum. Can the neuron doctrine still support our actual knowledge on the cerebellar structural arrangement?
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Brain Res Rev,
66,
16-34.
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J.M.Churko,
Q.Shao,
X.Q.Gong,
K.J.Swoboda,
D.Bai,
J.Sampson,
and
D.W.Laird
(2011).
Human dermal fibroblasts derived from oculodentodigital dysplasia patients suggest that patients may have wound-healing defects.
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Hum Mutat,
32,
456-466.
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M.Schütz,
T.Auth,
A.Gehrt,
F.Bosen,
I.Körber,
N.Strenzke,
T.Moser,
and
K.Willecke
(2011).
The connexin26 S17F mouse mutant represents a model for the human hereditary keratitis-ichthyosis-deafness syndrome.
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Hum Mol Genet,
20,
28-39.
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N.Bazazzadegan,
A.M.Sheffield,
M.Sobhani,
K.Kahrizi,
N.C.Meyer,
G.Van Camp,
N.Hilgert,
S.S.Abedini,
F.Habibi,
A.Daneshi,
C.Nishimura,
M.R.Avenarius,
M.Farhadi,
R.J.Smith,
and
H.Najmabadi
(2011).
Two Iranian families with a novel mutation in GJB2 causing autosomal dominant nonsyndromic hearing loss.
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Am J Med Genet A,
155,
1202-1211.
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R.M.Mroue,
M.E.El-Sabban,
and
R.S.Talhouk
(2011).
Connexins and the gap in context.
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Integr Biol (Camb),
3,
255-266.
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S.Maeda,
and
T.Tsukihara
(2011).
Structure of the gap junction channel and its implications for its biological functions.
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Cell Mol Life Sci,
68,
1115-1129.
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U.Koppelhus,
L.Tranebjaerg,
G.Esberg,
M.Ramsing,
M.Lodahl,
N.D.Rendtorff,
H.V.Olesen,
and
M.Sommerlund
(2011).
A novel mutation in the connexin 26 gene (GJB2) in a child with clinical and histological features of keratitis-ichthyosis-deafness (KID) syndrome.
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Clin Exp Dermatol,
36,
142-148.
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Y.Chen,
Y.Zhou,
X.Lin,
H.C.Wong,
Q.Xu,
J.Jiang,
S.Wang,
M.M.Lurtz,
C.F.Louis,
R.D.Veenstra,
and
J.J.Yang
(2011).
Molecular interaction and functional regulation of connexin50 gap junctions by calmodulin.
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Biochem J,
435,
711-722.
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Y.Ohta,
K.Nishikawa,
Y.Hiroaki,
and
Y.Fujiyoshi
(2011).
Electron tomographic analysis of gap junctions in lateral giant fibers of crayfish.
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J Struct Biol,
175,
49-61.
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B.Olshansky,
M.Delmar,
and
G.F.Tomaselli
(2010).
The year in arrhythmias--2009: part I.
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Heart Rhythm,
7,
417-426.
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B.P.Pedersen,
J.P.Morth,
and
P.Nissen
(2010).
Structure determination using poorly diffracting membrane-protein crystals: the H+-ATPase and Na+,K+-ATPase case history.
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Acta Crystallogr D Biol Crystallogr,
66,
309-313.
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C.Ambrosi,
D.Boassa,
J.Pranskevich,
A.Smock,
A.Oshima,
J.Xu,
B.J.Nicholson,
and
G.E.Sosinsky
(2010).
Analysis of four connexin26 mutant gap junctions and hemichannels reveals variations in hexamer stability.
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Biophys J,
98,
1809-1819.
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D.W.Laird
(2010).
The gap junction proteome and its relationship to disease.
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Trends Cell Biol,
20,
92.
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H.A.Sánchez,
G.Mese,
M.Srinivas,
T.W.White,
and
V.K.Verselis
(2010).
Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome.
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J Gen Physiol,
136,
47-62.
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J.A.Lundbaek,
S.A.Collingwood,
H.I.Ingólfsson,
R.Kapoor,
and
O.S.Andersen
(2010).
Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes.
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J R Soc Interface,
7,
373-395.
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J.Wang,
and
G.Dahl
(2010).
SCAM analysis of Panx1 suggests a peculiar pore structure.
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J Gen Physiol,
136,
515-527.
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K.R.Vinothkumar,
and
R.Henderson
(2010).
Structures of membrane proteins.
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Q Rev Biophys,
43,
65.
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K.Yoshimura,
and
M.Sokabe
(2010).
Mechanosensitivity of ion channels based on protein-lipid interactions.
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J R Soc Interface,
7,
S307-S320.
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M.A.Retamal,
S.Yin,
G.A.Altenberg,
and
L.Reuss
(2010).
Voltage-dependent facilitation of Cx46 hemichannels.
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Am J Physiol Cell Physiol,
298,
C132-C139.
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M.Kalman,
and
N.Ben-Tal
(2010).
Quality assessment of protein model-structures using evolutionary conservation.
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Bioinformatics,
26,
1299-1307.
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M.Schütz,
P.Scimemi,
P.Majumder,
R.D.De Siati,
G.Crispino,
L.Rodriguez,
M.Bortolozzi,
R.Santarelli,
A.Seydel,
S.Sonntag,
N.Ingham,
K.P.Steel,
K.Willecke,
and
F.Mammano
(2010).
The human deafness-associated connexin 30 T5M mutation causes mild hearing loss and reduces biochemical coupling among cochlear non-sensory cells in knock-in mice.
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Hum Mol Genet,
19,
4759-4773.
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P.Majumder,
G.Crispino,
L.Rodriguez,
C.D.Ciubotaru,
F.Anselmi,
V.Piazza,
M.Bortolozzi,
and
F.Mammano
(2010).
ATP-mediated cell-cell signaling in the organ of Corti: the role of connexin channels.
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Purinergic Signal,
6,
167-187.
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R.Grosely,
F.Kieken,
and
P.L.Sorgen
(2010).
Optimizing the solution conditions to solve the structure of the Connexin43 carboxyl terminus attached to the 4(th) transmembrane domain in detergent micelles.
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Cell Commun Adhes,
17,
23-33.
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S.Nakagawa,
S.Maeda,
and
T.Tsukihara
(2010).
Structural and functional studies of gap junction channels.
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Curr Opin Struct Biol,
20,
423-430.
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S.W.Yum,
J.Zhang,
and
S.S.Scherer
(2010).
Dominant connexin26 mutants associated with human hearing loss have trans-dominant effects on connexin30.
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Neurobiol Dis,
38,
226-236.
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A.G.Lee
(2009).
The effects of lipids on channel function.
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J Biol,
8,
86.
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A.L.Harris
(2009).
Gating on the outside.
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J Gen Physiol,
133,
549-553.
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C.D'hondt,
R.Ponsaerts,
H.De Smedt,
G.Bultynck,
and
B.Himpens
(2009).
Pannexins, distant relatives of the connexin family with specific cellular functions?
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Bioessays,
31,
953-974.
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D.A.Goodenough,
and
D.L.Paul
(2009).
Gap junctions.
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Cold Spring Harbor Perspect Biol,
1,
a002576.
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D.Locke,
and
A.L.Harris
(2009).
Connexin channels and phospholipids: association and modulation.
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BMC Biol,
7,
52.
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D.Locke,
S.Bian,
H.Li,
and
A.L.Harris
(2009).
Post-translational modifications of connexin26 revealed by mass spectrometry.
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Biochem J,
424,
385-398.
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G.G.Hesketh,
J.E.Van Eyk,
and
G.F.Tomaselli
(2009).
Mechanisms of gap junction traffic in health and disease.
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J Cardiovasc Pharmacol,
54,
263-272.
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J.W.Kyle,
V.M.Berthoud,
J.Kurutz,
P.J.Minogue,
M.Greenspan,
D.A.Hanck,
and
E.C.Beyer
(2009).
The N terminus of connexin37 contains an alpha-helix that is required for channel function.
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J Biol Chem,
284,
20418-20427.
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M.Freigassner,
H.Pichler,
and
A.Glieder
(2009).
wTuning microbial hosts for membrane protein production.
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Microb Cell Fact,
8,
69.
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M.Suga,
S.Maeda,
S.Nakagawa,
E.Yamashita,
and
T.Tsukihara
(2009).
A description of the structural determination procedures of a gap junction channel at 3.5 A resolution.
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Acta Crystallogr D Biol Crystallogr,
65,
758-766.
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Q.Tang,
T.L.Dowd,
V.K.Verselis,
and
T.A.Bargiello
(2009).
Conformational changes in a pore-forming region underlie voltage-dependent "loop gating" of an unapposed connexin hemichannel.
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J Gen Physiol,
133,
555-570.
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S.Johnstone,
B.Isakson,
and
D.Locke
(2009).
Biological and biophysical properties of vascular connexin channels.
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Int Rev Cell Mol Biol,
278,
69.
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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.
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Links
