spacer
spacer

PDBsum entry 2zw3

Go to PDB code: 
protein Protein-protein interface(s) links
Cell adhesion PDB id
2zw3
Jmol
Contents
Protein chains
(+ 0 more) 201 a.a. *
* Residue conservation analysis
PDB id:
2zw3
Name: Cell adhesion
Title: Structure of the connexin-26 gap junction channel at 3.5 angstrom resolution
Structure: Gap junction beta-2 protein. Chain: a, b, c, d, e, f. Synonym: connexin-26, cx26. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
3.50Å     R-factor:   0.338     R-free:   0.351
Authors: S.Maeda,S.Nakagawa,M.Suga,E.Yamashita,A.Oshima,Y.Fujiyoshi, T.Tsukihara
Key ref:
S.Maeda et al. (2009). Structure of the connexin 26 gap junction channel at 3.5 A resolution. Nature, 458, 597-602. PubMed id: 19340074 DOI: 10.1038/nature07869
Date:
01-Dec-08     Release date:   07-Apr-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P29033  (CXB2_HUMAN) -  Gap junction beta-2 protein
Seq:
Struc:
226 a.a.
201 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   9 terms 
  Biological process     cell communication   14 terms 
  Biochemical function     gap junction channel activity     1 term  

 

 
DOI no: 10.1038/nature07869 Nature 458:597-602 (2009)
PubMed id: 19340074  
 
 
Structure of the connexin 26 gap junction channel at 3.5 A resolution.
S.Maeda, S.Nakagawa, M.Suga, E.Yamashita, A.Oshima, Y.Fujiyoshi, T.Tsukihara.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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.
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).
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2009, 458, 597-602) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21348854 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.
  Biochem J, 436, 35-43.  
20621648 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?
  Brain Res Rev, 66, 16-34.  
  21305658 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.
  Hum Mutat, 32, 456-466.  
20926451 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.
  Hum Mol Genet, 20, 28-39.  
  21484990 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.
  Am J Med Genet A, 155, 1202-1211.  
21437329 R.M.Mroue, M.E.El-Sabban, and R.S.Talhouk (2011).
Connexins and the gap in context.
  Integr Biol (Camb), 3, 255-266.  
20960023 S.Maeda, and T.Tsukihara (2011).
Structure of the gap junction channel and its implications for its biological functions.
  Cell Mol Life Sci, 68, 1115-1129.  
20846357 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.
  Clin Exp Dermatol, 36, 142-148.  
21320072 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.
  Biochem J, 435, 711-722.  
21514388 Y.Ohta, K.Nishikawa, Y.Hiroaki, and Y.Fujiyoshi (2011).
Electron tomographic analysis of gap junctions in lateral giant fibers of crayfish.
  J Struct Biol, 175, 49-61.  
20185116 B.Olshansky, M.Delmar, and G.F.Tomaselli (2010).
The year in arrhythmias--2009: part I.
  Heart Rhythm, 7, 417-426.  
20179343 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.
  Acta Crystallogr D Biol Crystallogr, 66, 309-313.  
20441744 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.
  Biophys J, 98, 1809-1819.  
19944606 D.W.Laird (2010).
The gap junction proteome and its relationship to disease.
  Trends Cell Biol, 20, 92.  
  20584891 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.
  J Gen Physiol, 136, 47-62.  
19940001 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.
  J R Soc Interface, 7, 373-395.  
  20937692 J.Wang, and G.Dahl (2010).
SCAM analysis of Panx1 suggests a peculiar pore structure.
  J Gen Physiol, 136, 515-527.  
20667175 K.R.Vinothkumar, and R.Henderson (2010).
Structures of membrane proteins.
  Q Rev Biophys, 43, 65.  
20356872 K.Yoshimura, and M.Sokabe (2010).
Mechanosensitivity of ion channels based on protein-lipid interactions.
  J R Soc Interface, 7, S307-S320.  
19889966 M.A.Retamal, S.Yin, G.A.Altenberg, and L.Reuss (2010).
Voltage-dependent facilitation of Cx46 hemichannels.
  Am J Physiol Cell Physiol, 298, C132-C139.  
20385730 M.Kalman, and N.Ben-Tal (2010).
Quality assessment of protein model-structures using evolutionary conservation.
  Bioinformatics, 26, 1299-1307.  
20858605 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.
  Hum Mol Genet, 19, 4759-4773.  
  20806010 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.
  Purinergic Signal, 6, 167-187.  
  20513204 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.
  Cell Commun Adhes, 17, 23-33.  
20542681 S.Nakagawa, S.Maeda, and T.Tsukihara (2010).
Structural and functional studies of gap junction channels.
  Curr Opin Struct Biol, 20, 423-430.  
20096356 S.W.Yum, J.Zhang, and S.S.Scherer (2010).
Dominant connexin26 mutants associated with human hearing loss have trans-dominant effects on connexin30.
  Neurobiol Dis, 38, 226-236.  
19818162 A.G.Lee (2009).
The effects of lipids on channel function.
  J Biol, 8, 86.  
  19468073 A.L.Harris (2009).
Gating on the outside.
  J Gen Physiol, 133, 549-553.  
19644918 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?
  Bioessays, 31, 953-974.  
  20066080 D.A.Goodenough, and D.L.Paul (2009).
Gap junctions.
  Cold Spring Harbor Perspect Biol, 1, a002576.  
19686581 D.Locke, and A.L.Harris (2009).
Connexin channels and phospholipids: association and modulation.
  BMC Biol, 7, 52.  
19775242 D.Locke, S.Bian, H.Li, and A.L.Harris (2009).
Post-translational modifications of connexin26 revealed by mass spectrometry.
  Biochem J, 424, 385-398.  
19701097 G.G.Hesketh, J.E.Van Eyk, and G.F.Tomaselli (2009).
Mechanisms of gap junction traffic in health and disease.
  J Cardiovasc Pharmacol, 54, 263-272.  
19478091 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.
  J Biol Chem, 284, 20418-20427.  
20040113 M.Freigassner, H.Pichler, and A.Glieder (2009).
wTuning microbial hosts for membrane protein production.
  Microb Cell Fact, 8, 69.  
19622859 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.
  Acta Crystallogr D Biol Crystallogr, 65, 758-766.  
  19468074 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.
  J Gen Physiol, 133, 555-570.  
19815177 S.Johnstone, B.Isakson, and D.Locke (2009).
Biological and biophysical properties of vascular connexin channels.
  Int Rev Cell Mol Biol, 278, 69.  
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.