Lipid Insertion Domain Unfolding Regulates Protein Orientational Transition Behavior in a Lipid Bilayer

Kwan Hon Cheng, Liming Qiu, Sara Y Cheng, Mark Vaughn

Research output: Contribution to journalArticlepeer-review

Abstract

We have used coarse-grained (CG) and united atom (UA) molecular dynamics simulations to explore the mechanisms of protein orientational transition of a model peptide (A beta(42)) in a phosphatidylcholine/cholesterol (PC/CHO) lipid bilayer. We started with an inserted state of A beta(42) containing a folded (I) or unfolded (II) K28-A42 lipid insertion domain (LID), which was stabilized by the K28-snorkeling and A42-anchoring to the PC polar groups in the lipid bilayer. After a UA-to-CG transformation and a 1000 ns-CG simulation for enhancing the sampling of protein orientations, we discovered two transitions: I-to-"deep inserted" state with disrupted K28-snorkeling and II-to-"deep surface" state with disrupted A42-anchoring. The new states remained stable after a CG-to-UA transformation and a 200 ns-UA simulation relaxation. Significant changes in the cholesterol-binding domain of A beta(42) and protein-induced membrane disruptions were evident after the transitions. We propose that th
Original languageEnglish
Pages (from-to)22-39
JournalBiophysical Chemistry
DOIs
StatePublished - Nov 2015

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