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Protein-dependent membrane interaction of a partially disordered protein complex with oleic acid : Implications for cancer lipidomics

Chaudhuri, Arunima; Prasanna, Xavier; Agiru, Priyanka; Chakraborty, Hirak; Rydström, Anna LU ; Ho, James C S; Svanborg, Catharina LU ; Sengupta, Durba and Chattopadhyay, Amitabha (2016) In Scientific Reports 6.
Abstract

Bovine α-lactalbumin (BLA) forms cytotoxic complexes with oleic acid (OA) that perturbs tumor cell membranes, but molecular determinants of these membrane-interactions remain poorly understood. Here, we aim to obtain molecular insights into the interaction of BLA/BLA-OA complex with model membranes. We characterized the folding state of BLA-OA complex using tryptophan fluorescence and resolved residue-specific interactions of BLA with OA using molecular dynamics simulation. We integrated membrane-binding data using a voltage-sensitive probe and molecular dynamics (MD) to demonstrate the preferential interaction of the BLA-OA complex with negatively charged membranes. We identified amino acid residues of BLA and BLA-OA complex as... (More)

Bovine α-lactalbumin (BLA) forms cytotoxic complexes with oleic acid (OA) that perturbs tumor cell membranes, but molecular determinants of these membrane-interactions remain poorly understood. Here, we aim to obtain molecular insights into the interaction of BLA/BLA-OA complex with model membranes. We characterized the folding state of BLA-OA complex using tryptophan fluorescence and resolved residue-specific interactions of BLA with OA using molecular dynamics simulation. We integrated membrane-binding data using a voltage-sensitive probe and molecular dynamics (MD) to demonstrate the preferential interaction of the BLA-OA complex with negatively charged membranes. We identified amino acid residues of BLA and BLA-OA complex as determinants of these membrane interactions using MD, functionally corroborated by uptake of the corresponding α-LA peptides across tumor cell membranes. The results suggest that the α-LA component of these cytotoxic complexes confers specificity for tumor cell membranes through protein interactions that are maintained even in the lipid complex, in the presence of OA.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84991289637
  • wos:000384991300001
ISSN
2045-2322
DOI
10.1038/srep35015
language
English
LU publication?
yes
id
5d4d1228-885e-4e23-85fa-0f7999809d13
date added to LUP
2016-10-31 11:03:57
date last changed
2017-04-09 04:51:07
@article{5d4d1228-885e-4e23-85fa-0f7999809d13,
  abstract     = {<p>Bovine α-lactalbumin (BLA) forms cytotoxic complexes with oleic acid (OA) that perturbs tumor cell membranes, but molecular determinants of these membrane-interactions remain poorly understood. Here, we aim to obtain molecular insights into the interaction of BLA/BLA-OA complex with model membranes. We characterized the folding state of BLA-OA complex using tryptophan fluorescence and resolved residue-specific interactions of BLA with OA using molecular dynamics simulation. We integrated membrane-binding data using a voltage-sensitive probe and molecular dynamics (MD) to demonstrate the preferential interaction of the BLA-OA complex with negatively charged membranes. We identified amino acid residues of BLA and BLA-OA complex as determinants of these membrane interactions using MD, functionally corroborated by uptake of the corresponding α-LA peptides across tumor cell membranes. The results suggest that the α-LA component of these cytotoxic complexes confers specificity for tumor cell membranes through protein interactions that are maintained even in the lipid complex, in the presence of OA.</p>},
  articleno    = {35015},
  author       = {Chaudhuri, Arunima and Prasanna, Xavier and Agiru, Priyanka and Chakraborty, Hirak and Rydström, Anna and Ho, James C S and Svanborg, Catharina and Sengupta, Durba and Chattopadhyay, Amitabha},
  issn         = {2045-2322},
  language     = {eng},
  month        = {10},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Protein-dependent membrane interaction of a partially disordered protein complex with oleic acid : Implications for cancer lipidomics},
  url          = {http://dx.doi.org/10.1038/srep35015},
  volume       = {6},
  year         = {2016},
}