A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

Zhang, Xing; Lei, Dongsheng; Zhang, Lei; Rames, Matthew; Zhang, Shengli

doi:10.1371/journal.pone.0120233

Title: A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

Journal Article · Fri Mar 20 00:00:00 EDT 2015 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0120233· OSTI ID:1190954

Zhang, Xing ^[1]; Lei, Dongsheng ^[1]; Zhang, Lei ^[2]; Rames, Matthew ^[2]; Zhang, Shengli ^[3]

Xi'an Jiaotong Univ., Xi'an, Shaanxi (People's Republic of China); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Xi'an Jiaotong Univ., Xi'an, Shaanxi (People's Republic of China)

Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipidfree apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1190954

Journal Information:: PLoS ONE, Vol. 10, Issue 3; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 5 works

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