PMID- 25099799
OWN - NLM
STAT- MEDLINE
DCOM- 20150821
LR  - 20211021
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 107
IP  - 3
DP  - 2014 Aug 5
TI  - Characterization of a novel water pocket inside the human Cx26 hemichannel 
      structure.
PG  - 599-612
LID - S0006-3495(14)00601-8 [pii]
LID - 10.1016/j.bpj.2014.05.037 [doi]
AB  - Connexins (Cxs) are a family of vertebrate proteins constituents of gap junction 
      channels (GJCs) that connect the cytoplasm of adjacent cells by the end-to-end 
      docking of two Cx hemichannels. The intercellular transfer through GJCs occurs by 
      passive diffusion allowing the exchange of water, ions, and small molecules. 
      Despite the broad interest to understand, at the molecular level, the functional 
      state of Cx-based channels, there are still many unanswered questions regarding 
      structure-function relationships, perm-selectivity, and gating mechanisms. In 
      particular, the ordering, structure, and dynamics of water inside Cx GJCs and 
      hemichannels remains largely unexplored. In this work, we describe the 
      identification and characterization of a believed novel water pocket-termed the 
      IC pocket-located in-between the four transmembrane helices of each human Cx26 
      (hCx26) monomer at the intracellular (IC) side. Using molecular dynamics (MD) 
      simulations to characterize hCx26 internal water structure and dynamics, six IC 
      pockets were identified per hemichannel. A detailed characterization of the 
      dynamics and ordering of water including conformational variability of residues 
      forming the IC pockets, together with multiple sequence alignments, allowed us to 
      propose a functional role for this cavity. An in vitro assessment of tracer 
      uptake suggests that the IC pocket residue Arg-143 plays an essential role on the 
      modulation of the hCx26 hemichannel permeability.
CI  - Copyright (c) 2014 Biophysical Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Araya-Secchi, Raul
AU  - Araya-Secchi R
AD  - Computational Biology Lab (DLab), Fundacion Ciencia & Vida, Nunoa, Santiago; 
      Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown 
      Heights, New York; Centro Interdisciplinario de Neurociencias de Valparaiso 
      (CINV), Universidad de Valparaiso, Valparaiso.
FAU - Perez-Acle, Tomas
AU  - Perez-Acle T
AD  - Computational Biology Lab (DLab), Fundacion Ciencia & Vida, Nunoa, Santiago; 
      Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso. Electronic address: tomas@dlab.cl.
FAU - Kang, Seung-Gu
AU  - Kang SG
AD  - Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown 
      Heights, New York.
FAU - Huynh, Tien
AU  - Huynh T
AD  - Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown 
      Heights, New York.
FAU - Bernardin, Alejandro
AU  - Bernardin A
AD  - Computational Biology Lab (DLab), Fundacion Ciencia & Vida, Nunoa, Santiago; 
      Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso.
FAU - Escalona, Yerko
AU  - Escalona Y
AD  - Computational Biology Lab (DLab), Fundacion Ciencia & Vida, Nunoa, Santiago; 
      Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso.
FAU - Garate, Jose-Antonio
AU  - Garate JA
AD  - Computational Biology Lab (DLab), Fundacion Ciencia & Vida, Nunoa, Santiago; 
      Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso.
FAU - Martinez, Agustin D
AU  - Martinez AD
AD  - Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso.
FAU - Garcia, Isaac E
AU  - Garcia IE
AD  - Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso.
FAU - Saez, Juan C
AU  - Saez JC
AD  - Centro Interdisciplinario de Neurociencias de Valparaiso (CINV), Universidad de 
      Valparaiso, Valparaiso; Departamento de Fisiologia, Facultad de Ciencias 
      Biologicas, Pontificia Universidad Catolica de Chile, Santiago.
FAU - Zhou, Ruhong
AU  - Zhou R
AD  - Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown 
      Heights, New York. Electronic address: ruhongz@us.ibm.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (Connexins)
RN  - 0 (GJB2 protein, human)
RN  - 059QF0KO0R (Water)
RN  - 127120-53-0 (Connexin 26)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Connexin 26
MH  - Connexins/*chemistry/metabolism
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Molecular Sequence Data
MH  - Water/*chemistry/metabolism
PMC - PMC4129493
EDAT- 2014/08/08 06:00
MHDA- 2015/08/22 06:00
PMCR- 2015/08/05
CRDT- 2014/08/08 06:00
PHST- 2013/11/04 00:00 [received]
PHST- 2014/05/12 00:00 [revised]
PHST- 2014/05/14 00:00 [accepted]
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/08/22 06:00 [medline]
PHST- 2015/08/05 00:00 [pmc-release]
AID - S0006-3495(14)00601-8 [pii]
AID - 10.1016/j.bpj.2014.05.037 [doi]
PST - ppublish
SO  - Biophys J. 2014 Aug 5;107(3):599-612. doi: 10.1016/j.bpj.2014.05.037.