Structure of HDL: particle subclasses and molecular components.

Area of Science:

• Lipid Metabolism
• Proteomics
• Structural Biology

Background:

• High-density lipoprotein (HDL) plays a crucial role in lipid transport and cardiovascular health.
• Understanding HDL's molecular intricacies is vital for grasping its interactions with plasma factors and cell-surface proteins involved in its metabolism.
• HDL particles exhibit significant heterogeneity in physical, chemical, and biological properties, complicating structural analysis.

Purpose of the Study:

• To review current knowledge on the composition, structure, and heterogeneity of human plasma HDL.
• To discuss the multifaceted HDL proteome, lipidome, and subclasses.
• To present putative models of HDL particle structure and the history of structural studies.

Main Methods:

• Review of existing literature on HDL structure and composition.
• Analysis of data from various low-resolution techniques, including mass spectrometry.
• Discussion of molecular dynamics simulations and historical structural studies.

Main Results:

• HDL particles are characterized by complex and diverse proteomic and lipidomic compositions.
• Multiple major protein isoforms, including post-translationally modified variants, contribute to HDL's heterogeneity.
• Various HDL subclasses exist, with ongoing efforts to elucidate their distinct structures and functions.

Conclusions:

• Despite challenges in high-resolution structural determination, a general understanding of HDL structure is emerging from diverse methodologies.
• Elucidating HDL's molecular structure is essential for a comprehensive understanding of its biological roles.
• Continued research utilizing advanced techniques will further refine models of HDL particle structure and function.