title: Protein-dependent Membrane Interaction of A Partially Disordered Protein Complex with Oleic Acid: Implications for Cancer Lipidomics.
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 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.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Arunima
authors.initials: A
authors.lastname: Chaudhuri
authors.affiliation: CSIR-National Chemical Laboratory, Pune 411 008, India.
authors.forename: Xavier
authors.initials: X
authors.lastname: Prasanna
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Agiru
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Hirak
authors.initials: H
authors.lastname: Chakraborty
authors.affiliation: Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rydström
authors.affiliation: Centre for Biomimetic Sensor Science, School of Materials Science &Engineering, Nanyang Technological University, 637553 Singapore.
authors.forename: James C S
authors.initials: JC
authors.lastname: Ho
authors.affiliation: Department of Microbiology, Immunology and Glycobiology (MIG), Institute of Laboratory Medicine, Lund University, Lund, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Svanborg
authors.affiliation: CSIR-National Chemical Laboratory, Pune 411 008, India.
authors.forename: Durba
authors.initials: D
authors.lastname: Sengupta
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D000072283:A549 Cells; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
chemical_list: D046912:Multiprotein Complexes; D019301:Oleic Acid; D014364:Tryptophan; D007768:Lactalbumin