Protein-dependent membrane interaction of a partially disordered protein complex with oleic acid : Implications for cancer lipidomics
(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
- Chaudhuri, Arunima ; Prasanna, Xavier ; Agiru, Priyanka ; Chakraborty, Hirak ; Rydström, Anna LU ; Ho, James C S ; Svanborg, Catharina LU ; Sengupta, Durba and Chattopadhyay, Amitabha
- organization
- publishing date
- 2016-10-12
- 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
- 2024-06-14 16:37:44
@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}}, }