Publication: Amyloid seeding by oxidized apolipoprotein A-I

Congratulations to collaborator Giorgio Cavigiolio, his group at CHORI (Children’s Hospital Oakland Research Institute), and Jennifer Boatz on the publication of our new collaborative paper. It reports functional and structural studies of the effect of oxidation on apolipoprotein A-I (ApoA1), using a variety of experiments and assays – including solid-state NMR. Oxidation of the protein causes it to become more monomeric and also less stably folded. As a consequence it becomes prone to aggregation into amyloid-like fibrils. Interestingly, these oxidized aggregates are able to subvert non-oxidized protein into an amyloidogenic (i.e. aggregation-prone) state. Another interesting aspect of these aggregated proteins is that they may feature a typical amyloid core structure composed of β-sheets, but that large parts of the protein stay outside this core structure. These latter “flanking”domains retain much of their native α-helical fold, somewhat reminiscent of our prior findings in the Huntington’s disease protein. We hypothesize that these non-amyloid domains may mediate interactions not only within the fibrils but also between fibrils and still-soluble native proteins. The paper also discusses the potential role of these molecular processes in atherosclerosis.

The paper:
Andrzej Witkowski, Gary K. L. Chan, Jennifer C. Boatz, Nancy J. Li, Ayuka P. Inoue, Jaclyn C. Wong, Patrick C. A. van der Wel, and Giorgio Cavigiolio (2018) “Methionine oxidized apolipoprotein A-I at the crossroads of HDL biogenesis and amyloid formation” FASEB Journal, in press. Online at the journal, and also on PubMed.