PMID- 24642864
OWN - NLM
STAT- MEDLINE
DCOM- 20141219
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 3
DP  - 2014
TI  - Cysteine residues impact the stability and micelle interaction dynamics of the 
      human mitochondrial beta-barrel anion channel hVDAC-2.
PG  - e92183
LID - 10.1371/journal.pone.0092183 [doi]
LID - e92183
AB  - The anti-apoptotic 19-stranded transmembrane human voltage dependent anion 
      channel isoform 2 (hVDAC-2) beta-barrel stability is crucial for anion transport in 
      mitochondria. The role of the unusually high number of cysteine residues in this 
      isoform is poorly understood. Using a Cys-less construct of hVDAC-2, we have 
      investigated the contribution of cysteines to channel function, barrel stability 
      and its influence on the strength of protein-micelle interactions. We observe 
      that despite the overall preservation in barrel structure upon cysteine mutation, 
      subtle local variations in the mode of interaction of the barrel with its 
      refolded micellar environment arise, which may manifest itself in the channel 
      activity of both the proteins.Fluorescence measurements of the Trp residues in 
      hVDAC-2 point to possible differences in the association of the barrel with 
      lauryldimethylamine oxide (LDAO) micelles. Upon replacement of cysteines in 
      hVDAC-2, our data suggests greater barrel rigidity by way of intra-protein 
      interactions. This, in turn, lowers the equilibrium barrel thermodynamic 
      parameters in LDAOby perturbing the stability of the protein-micelle complex. In 
      addition to this, we also find a difference in the cooperativity of unfolding 
      upon increasing the LDAO concentration, implying the importance of micelle 
      concentration and micelle-protein ratios on the stability of this barrel. Our 
      results indicate that the nine cysteine residues of hVDAC-2 are the key in 
      establishing strong(er) barrel interactions with its environment and also impart 
      additional malleability to the barrel scaffold.
FAU - Maurya, Svetlana Rajkumar
AU  - Maurya SR
AD  - Molecular Biophysics Laboratory, Department of Biological Sciences, Indian 
      Institute of Science Education and Research, Bhopal, Madhya Pradesh, India.
FAU - Mahalakshmi, Radhakrishnan
AU  - Mahalakshmi R
AD  - Molecular Biophysics Laboratory, Department of Biological Sciences, Indian 
      Institute of Science Education and Research, Bhopal, Madhya Pradesh, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140318
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Dimethylamines)
RN  - 0 (Micelles)
RN  - 0 (Protein Isoforms)
RN  - 0 (Recombinant Proteins)
RN  - 0 (VDAC2 protein, human)
RN  - 0 (Voltage-Dependent Anion Channel 2)
RN  - 4F6FC4MI8W (dodecyldimethylamine oxide)
RN  - 8DUH1N11BX (Tryptophan)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Amino Acid Substitution
MH  - Cysteine/*chemistry/genetics
MH  - Dimethylamines/chemistry
MH  - Escherichia coli/genetics/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Micelles
MH  - Mitochondria/*chemistry/metabolism
MH  - Models, Molecular
MH  - Protein Folding
MH  - Protein Isoforms/chemistry/genetics/metabolism
MH  - Protein Stability
MH  - Protein Structure, Secondary
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Thermodynamics
MH  - Tryptophan/chemistry/genetics
MH  - Voltage-Dependent Anion Channel 2/*chemistry/genetics/metabolism
PMC - PMC3967697
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/03/20 06:00
MHDA- 2014/12/20 06:00
PMCR- 2014/03/18
CRDT- 2014/03/20 06:00
PHST- 2013/12/18 00:00 [received]
PHST- 2014/02/20 00:00 [accepted]
PHST- 2014/03/20 06:00 [entrez]
PHST- 2014/03/20 06:00 [pubmed]
PHST- 2014/12/20 06:00 [medline]
PHST- 2014/03/18 00:00 [pmc-release]
AID - PONE-D-13-53437 [pii]
AID - 10.1371/journal.pone.0092183 [doi]
PST - epublish
SO  - PLoS One. 2014 Mar 18;9(3):e92183. doi: 10.1371/journal.pone.0092183. eCollection 
      2014.