Linked Life Data

17387661

Source:http://linkedlifedata.com/resource/pubmed/id/17387661

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-4-30
pubmed:abstractText
Mitochondrial porin or VDAC (voltage-dependent anion-selective channel) is the most abundant protein in the mitochondrial outer membrane. The structure of VDAC has been predicted to be a transmembrane beta-barrel with an alpha-helix at the N terminus. It is a matter of debate as to whether this putative alpha-helix plays a structural role as a component of the pore walls or a function in the pore activity. We have synthesised the human VDAC1 (HVDAC1) N-terminal peptide Ac-AVPPTYADLGKSARDVFTK-NH2 (Prn2-20) and determined its structure by CD and NMR spectroscopy. CD studies show that the Prn2-20 peptide exists in aqueous solvent as an unstructured peptide with no stable secondary structure. In membrane-mimetic SDS micelles or water/trifluoroethanol, however, it assumes an amphipathic alpha-helix conformation between Tyr5 and Val16, as deduced from NMR. No ordered structure was observed in dodecyl beta-maltoside. Differential scanning calorimetric measurements were carried out in order to examine the membrane affinity of the peptide. Upon interaction with the negatively charged 1,2 dipalmitoyl-sn-glycero-3-phosphoserine membrane, Prn2-20 exhibited distinctive behaviour, suggesting that electrostatics play an important role. Interaction between the peptide and artificial bilayers indicates that the peptide lies on the membrane surface. Recombinant HVDAC1 deletion mutants, devoid of seven or 19 N-terminal amino acids, were used for transfection of eukaryotic cells. Over-expression of HVDAC1 increases the number of Cos cells with depolarised mitochondria, and this effect is progressively reduced in cells transfected with HVDAC1 lacking those seven or 19 amino acids. The mitochondrial targeting of the deletion mutants is unaffected. The overall picture emerging from our experiments is that the VDAC N-terminal peptide plays a role in the proper function of this protein during apoptotic events.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1439-4227
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
744-56
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Determination of the conformation of the human VDAC1 N-terminal peptide, a protein moiety essential for the functional properties of the pore.
pubmed:affiliation
Department of Chemical Sciences, Laboratory of Molecular Biology, University of Catania, Viale A. Doria, 6, 95125 Catania, Italy. vdpbiofa@unict.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't