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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
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
article number
35015
publisher
Nature Publishing Group
external identifiers
  • pmid:27731329
  • wos:000384991300001
  • scopus:84991289637
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
2025-04-04 15:08:46
@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>}},
  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}},
  doi          = {{10.1038/srep35015}},
  volume       = {{6}},
  year         = {{2016}},
}