Dataset Information

Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation.

ABSTRACT: Single-molecule force spectroscopy methods, such as AFM and magnetic tweezers, have proved extremely beneficial in elucidating folding pathways for soluble and membrane proteins. To identify factors that determine the force rupture levels in force-induced membrane protein unfolding, we applied our near-atomic-level Upside molecular dynamics package to study the vertical and lateral pulling of bacteriorhodopsin (bR) and GlpG, respectively. With our algorithm, we were able to selectively alter the magnitudes of individual interaction terms and identify that, for vertical pulling, hydrogen bond strength had the strongest effect, whereas other non-bonded protein and membrane-protein interactions had only moderate influences, except for the extraction of the last helix where the membrane-protein interactions had a stronger influence. The up-down topology of the transmembrane helices caused helices to be pulled out as pairs. The rate-limiting rupture event often was the loss of H-bonds and the ejection of the first helix, which then propagated tension to the second helix, which rapidly exited the bilayer. The pulling of the charged linkers across the membrane had minimal influence, as did changing the bilayer thickness. For the lateral pulling of GlpG, the rate-limiting rupture corresponded to the separation of the helices within the membrane, with the H-bonds generally being broken only afterward. Beyond providing a detailed picture of the rupture events, our study emphasizes that the pulling mode greatly affects the factors that determine the forces needed to unfold a membrane protein.

SUBMITTER: Faruk NF

PROVIDER: S-EPMC9917119 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation.

Faruk Nabil F NF Peng Xiangda X Sosnick Tobin R TR

International journal of molecular sciences 20230131 3

Single-molecule force spectroscopy methods, such as AFM and magnetic tweezers, have proved extremely beneficial in elucidating folding pathways for soluble and membrane proteins. To identify factors that determine the force rupture levels in force-induced membrane protein unfolding, we applied our near-atomic-level <i>Upside</i> molecular dynamics package to study the vertical and lateral pulling of bacteriorhodopsin (bR) and GlpG, respectively. With our algorithm, we were able to selectively al ...[more]

PMID: 36768981

Similar Datasets

Project description:Hippocampal atrophy is a well-known feature of age-related memory decline, and hippocampal subfields may contribute differently to this decline. In this cross-sectional study, we investigated the associations between hippocampal subfield volumes and performance in free recall and recognition memory tasks in both verbal and visual modalities in older adults without dementia. We collected MRIs from 97 (41 males) right-handed participants aged over 60. We segmented the right and left hippocampi into (i) dentate gyrus and cornu ammonis 4 (DG/CA4); (ii) CA2 and CA3 (CA2/CA3); (iii) CA1; (iv) strata radiatum, lacunosum and moleculare; and (v) subiculum. Memory was assessed with verbal free recall and recognition tasks, as well as visual free recall and recognition tasks. Amyloid-β and hippocampal tau positivity were assessed using [18F]AZD4694 and [18F]MK6240 PET tracers, respectively. The verbal free recall and verbal recognition performances were positively associated with CA1 and strata radiatum, lacunosum and moleculare volumes. The verbal free recall and visual free recall were positively correlated with the right DG/CA4. The visual free recall, but not verbal free recall, was also associated with the right CA2/CA3. The visual recognition was not significantly associated with any subfield volume. Hippocampal tau positivity, but not amyloid-β positivity, was associated with reduced DG/CA4, CA2/CA3 and strata radiatum, lacunosum and moleculare volumes. Our results suggest that memory performances are linked to specific subfields. CA1 appears to contribute to the verbal modality, irrespective of the free recall or recognition mode of retrieval. In contrast, DG/CA4 seems to be involved in the free recall mode, irrespective of verbal or visual modalities. These results are concordant with the view that DG/CA4 plays a primary role in encoding a stimulus' distinctive attributes, and that CA2/CA3 could be instrumental in recollecting a visual memory from one of its fragments. Overall, we show that hippocampal subfield segmentation can be useful for detecting early volume changes and improve our understanding of the hippocampal subfields' roles in memory.

Dataset Information

Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation.

Publications

Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets