Crystal Structure of C-terminal Truncated Apolipoprotein A-I Reveals the Assembly of High Density Lipoprotein (HDL) by Dimerization

Small-angle X-ray Scattering of Apolipoprotein A-IV Reveals the Importance of Its Termini for Structural Stability

“…Recent structural studies have illuminated how apolipoproteins transition between monomers and dimers, revealing a novel helix-swapping mechanism (4,6). However, by necessity, both structures were derived from truncated proteins, thus raising questions about what effect the missing components have on the overall structure and whether they are good structural models for apolipoproteins in solution.…”

“…), thus making them difficult to characterize structurally (3). Although some success has been obtained using site-directed mutagenesis to stabilize particular oligomeric forms of apoA-I and apoE, this approach has the drawback of potentially altering protein conformation along with self-association state (4,5). We recently demonstrated that lipid-free human apoA-IV distributes predominantly between monomers and dimers and that their interconversion is slow enough that they can be isolated and studied individually (6).…”

ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease

“…44 Regarding the N-terminal region, there are data showing that this region can fold back on itself with the degree that depends on the particle size. 45,46 In larger HDL particles (9.6 nm), the helical structure of ApoA1 is well organized. The region involving 125-18 a.a. represents as a disordered loop that either interacts with the phospholipid bilayer or is exposed outside the particle.…”

Improving the diffraction of apoA-IV crystals through extreme dehydration

“…Apolipoproteins are highly helical and are thought to adopt a helical bundle in the free state and to undergo self-association into higher order oligomers (Weinberg & Spector, 1985;Garai & Frieden, 2010;Vitello & Scanu, 1976). This feature has hindered high-resolution structural studies and few structures of apolipoproteins are available (Borhani et al, 1997;Hatters et al, 2005;Mei & Atkinson, 2011). In the lipid-bound state, the evidence supports a general model in which two molecules wrap around a discoidal lipid bilayer (Segrest et al, 1999;Wu et al, 2007;Bhat et al, 2005).…”