Detection of apolipoprotein B100 early conformational changes during oxidation

Area of Science:

• Biochemistry
• Molecular Biology
• Cardiovascular Research

Background:

• Low-density lipoproteins (LDL) carry cholesterol, and their oxidation is implicated in atherosclerosis.
• Apolipoprotein B100 (apoB) is the main protein component of LDL, crucial for its structure and function.
• Understanding apoB modifications during LDL oxidation is key to elucidating atherogenic processes.

Purpose of the Study:

• To investigate the conformational changes of human plasma apoB during LDL oxidation.
• To focus on the early stages of LDL oxidation and apoB modification.
• To correlate apoB conformational dynamics with different phases of LDL oxidation.

Main Methods:

• Utilized two distinct modes of LDL oxidation initiation.
• Employed attenuated total reflection infrared spectroscopy to study protein and phospholipid conformational changes.
• Applied fluorescence spectroscopy to analyze surface monolayer dynamics.

Main Results:

• Conformational changes in apoB were observed even in the earliest stages of LDL oxidation.
• These early changes were predominantly located in the beta-sheet regions of apoB.
• LDL particle surface accessibility and mobility initially increased, then decreased during propagation, and increased again during decomposition phases of oxidation.

Conclusions:

• ApoB undergoes significant conformational alterations from the onset of LDL oxidation.
• The beta-sheet regions of apoB are particularly sensitive to early oxidative modifications.
• The dynamic changes in LDL surface properties reflect distinct phases of the oxidation process, offering new insights into LDL modification.