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: Arunima Chaudhuri, Xavier Prasanna, Priyanka Agiru, Hirak Chakraborty, Anna Rydström, James C S Ho, Catharina Svanborg, Durba Sengupta, Amitabha Chattopadhyay
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 35015 (10 12 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27731329 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Multiprotein Complexes
• Oleic Acid
• Tryptophan
• Lactalbumin

Topics

• A549 Cells
• Animals
• Binding Sites
• Cattle
• Cell Membrane (metabolism)
• Humans
• Lactalbumin (chemistry, metabolism)
• Models, Molecular
• Molecular Dynamics Simulation
• Multiprotein Complexes (chemistry, metabolism)
• Neoplasms (metabolism)
• Oleic Acid (metabolism)
• Protein Binding
• Protein Conformation
• Protein Folding
• Spectrometry, Fluorescence
• Tryptophan (chemistry)