Calcium-induced transformation of cardiolipin nanodisks

Autor: Patricia Ellison, Colin A. Fox, Nikita Ikon, Robert O. Ryan
Rok vydání: 2019
Předmět:
Zdroj: Biochim Biophys Acta Biomembr
ISSN: 0005-2736
DOI: 10.1016/j.bbamem.2019.03.005
Popis: Miniature membranes comprised of tetramyristoylcardiolipin (CL) and apolipoprotein (apo) A-I, termed nanodisks (ND), are stable, aqueous soluble, reconstituted high density lipoproteins. When CL ND, but not dimyristoylphosphatidylcholine (PC) ND, were incubated with CaCl(2), a concentration dependent increase in sample turbidity occurred, consistent with CL undergoing a bilayer to non-bilayer transition. To assess the cation specificity of this reaction, CL ND were incubated with various mono- and divalent cations. Whereas monovalent cations had no discernable effect, MgCl(2) and SrCl(2) induced a response similar to CaCl(2). When ND were formulated using different weight ratios of CL and PC, those possessing 100% CL or 75% CL remained susceptible to CaCl(2) induced sample turbidity development while ND possessing 50% CL displayed reduced susceptibility. ND comprised of 25 % CL and 75 % PC were unaffected by CaCl(2) under these conditions. SDS PAGE analysis of insoluble material generated by incubation of CL ND with CaCl(2) revealed that nearly all apoA-I was recovered in the insoluble fraction along with CL. One h after addition of EDTA to CaCl(2)-treated CL ND, sample clarity was restored. Collectively, the data are consistent with a model wherein Ca(2+) forms a bidentate interaction with anionic phosphates in the polar head group of CL. As phosphate group repositioning occurs to maximize Ca(2+) binding, CL acyl chains reposition, accentuating the conical shape of CL to an extent that is incompatible with the ND bilayer structure.
Databáze: OpenAIRE