HDL WITH SOF

Baylor College Of Medicine, Houston TX

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Human plasma high-density lipoproteins (HDL), the primary vehicle for reverse cholesterol transport, are the target of serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes that turns serum opaque. HDL comprises a core of neutral lipids, cholesteryl esters and some triglycerides, surrounded by a surface monolayer of cholesterol, phospholipids, and specialized proteins [apolipoproteins (apos) A-I and A-II]. A HDL is an unstable particle residing in a kinetic trap from which it can escape via chaotropic, detergent, or thermal perturbation. Recombinant (r) SOF catalyzes the transfer of nearly all neutral lipids of ~100,000 HDL particles (D ~ 8.5 nm) into a single, large cholesteryl ester-rich microemulsion (CERM;D >100 nm), leaving a new HDL-like particle [neo HDL (D ~ 5.8 nm)] while releasing lipid-free (LF) apo A-I. CERM formation and apo A-I release have similar kinetics, suggesting parallel or rapid consecutive steps.