Dataset Information

Protein-dependent Membrane Interaction of A Partially Disordered Protein Complex with Oleic Acid: Implications for Cancer Lipidomics.

ABSTRACT: Bovine ?-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 ?-LA peptides across tumor cell membranes. The results suggest that the ?-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.

SUBMITTER: Chaudhuri A

PROVIDER: S-EPMC5059734 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Protein-dependent Membrane Interaction of A Partially Disordered Protein Complex with Oleic Acid: Implications for Cancer Lipidomics.

Chaudhuri Arunima A Prasanna Xavier X Agiru Priyanka P Chakraborty Hirak H Rydström Anna A Ho James C S JC Svanborg Catharina C Sengupta Durba D Chattopadhyay Amitabha A

Scientific reports 20161012

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 membran ...[more]

PMID: 27731329

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Project description:Proteins from the intrinsically disordered group (IDP) focus the attention of many researchers engaged in protein structure analysis. The main criteria used in their identification are lack of secondary structure and significant structural variability. This variability takes forms that cannot be identified in the X-ray technique. In the present study, different criteria were used to assess the status of IDP proteins and their fragments recognized as intrinsically disordered regions (IDRs). The status of the hydrophobic core in proteins identified as IDPs and in their complexes was assessed. The status of IDRs as components of the ordering structure resulting from the construction of the hydrophobic core was also assessed. The hydrophobic core is understood as a structure encompassing the entire molecule in the form of a centrally located high concentration of hydrophobicity and a shell with a gradually decreasing level of hydrophobicity until it reaches a level close to zero on the protein surface. It is a model assuming that the protein folding process follows a micellization pattern aiming at exposing polar residues on the surface, with the simultaneous isolation of hydrophobic amino acids from the polar aquatic environment. The use of the model of hydrophobicity distribution in proteins in the form of the 3D Gaussian distribution described on the protein particle introduces the possibility of assessing the degree of similarity to the assumed micelle-like distribution and also enables the identification of deviations and mismatch between the actual distribution and the idealized distribution. The FOD (fuzzy oil drop) model and its modified FOD-M version allow for the quantitative assessment of these differences and the assessment of the relationship of these areas to the protein function. In the present work, the sections of IDRs in protein complexes classified as IDPs are analyzed. The classification "disordered" in the structural sense (lack of secondary structure or high flexibility) does not always entail a mismatch with the structure of the hydrophobic core. Particularly, the interface area, often consisting of IDRs, in many analyzed complexes shows the compliance of the hydrophobicity distribution with the idealized distribution, which proves that matching to the structure of the hydrophobic core does not require secondary structure ordering.

Dataset Information

Protein-dependent Membrane Interaction of A Partially Disordered Protein Complex with Oleic Acid: Implications for Cancer Lipidomics.

Publications

Protein-dependent Membrane Interaction of A Partially Disordered Protein Complex with Oleic Acid: Implications for Cancer Lipidomics.

Similar Datasets

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