7.6 In 1997, Borhani et al.7 were able to crystallize an Nterminal
truncated form of lipid-free apoA-I. The Borhani
structure was roughly saddle shaped having many characteristics
similar to those proposed for apoA-I on recombinant
HDL (rHDL) particles. Smaller segments that often contain
proline, located between helical regions, are bent or kinked.7
These kinks may help apoA-I assume a curved conformation.
The article stirred new interest in the conformation of lipidbound
apoA-I. There was less interest in the in-solution
conformation of intact, lipid-free apoA-I, but two papers were
published in 2005 and 2006. The validity of the later paper has
been questioned.8 However, the lipid-free solution structure
proposed by Silva et al.9 using chemical cross-linking combined
with mass spectrometry and sequence threading has many of
the features suggested by other biophysical studies.
Early studies of LCAT-deficient HDL suggested that the
first-formed HDL, nascent HDL or nHDL, was a lipid disk10
that carried two molecules of apoA-I. Jonas’s group perfected
the synthesis of synthetic particles using cholate dialysis,11 and
the properties of these particles have been studied for many
years. Early models agreed that apoA-I was located on the edge