synchrotron radiation circular dichroism spectroscopy reveals structural divergences in hdlbound apoai variants apolipoprotein ai apoai in highdensity lipoprotein hdl provides cardiovascular protection synchrotron radiation circular dichroism srcd spectroscopy was used to analyze the dynamic solution structure of the apoai protein in the apo and hdlstates and the protein structure conversion in hdl formation wildtype apoai protein was compared to human variants that either are protective r173c milano or lead to increased risk for ischaemic heart disease a164s comparable secondary structure distributions in the hdl particles including significant levels of beta strandturn were observed apoai milano in hdl displayed larger size heterogeneity increased protein flexibility and an altered lipidbinding profile whereas the apoai a164s in hdl showed decrease thermal stability potentially linking the intrinsic hdl propensities of the variants to disease risk