Lipids and Extracellular Materials

Dowhan, William

doi:10.1146/annurev-biochem-010314-112017

Cited by 9 publications

(11 citation statements)

References 10 publications

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“…The SMFS results indicate that in the absence of zwitterionic PE, anionic PG changes the folding free energy landscape of LacY in such a manner that both native and perturbed conformers are equally favored. In the presence of PE, the free energy landscape promotes the native LacY fold and suppresses the perturbed structure confirming that lipid-dependent topogenesis is primarily a thermodynamically driven process, as suggested (Bogdanov and Dowhan, 2012; Dowhan, 2014; Vitrac et al, 2013). …”

Section: Introductionsupporting

confidence: 61%

Observing a Lipid-Dependent Alteration in Single Lactose Permeases

et al. 2015

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SUMMARY Lipids of the Escherichia coli membrane are mainly composed of 70–80% phosphatidylethanolamine (PE) and 20–25% phosphatidylglycerol (PG). Biochemical studies indicate that the depletion of PE causes inversion of the N-terminal helix bundle of the lactose permease (LacY), and helix VII becomes extramembraneous. Here we study this phenomenon using single-molecule force spectroscopy, which is sensitive to the structure of membrane proteins. In PE and PG at a ratio of 3:1, ~95% of the LacY molecules adopt a native structure. However, when PE is omitted and the membrane contains PG only, LacY almost equally populates a native and a perturbed conformation. The most drastic changes occur at helices VI and VII and the intervening loop. Since helix VII contains Asp237 and Asp240, zwitterionic PE may suppress electrostatic repulsion between LacY and PG in the PE:PG environment. Thus, PE promotes a native fold and prevents LacY from populating a functionally defective, non-native conformation.

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Section: Introductionsupporting

confidence: 61%

Observing a Lipid-Dependent Alteration in Single Lactose Permeases

et al. 2015

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“…We used only phosphatidylcholine as a phospholipid, whereas the E. coli membrane consist of other phospholipids. Phospholipid composition has been reported to play an important role in determining the topology of membrane proteins58. Despite these differences, we have shown the efficacy of incorporating the Sec translocon in displaying various membrane proteins.…”

Section: Discussionmentioning

confidence: 75%

“…In addition, analyzing terminal tag-sequences alone cannot distinguish whether the detected increase in the fluorescence signal is due to topological changes of mPOIs, as with EmrE, or increased membrane integration. Additional analysis including protease protection assay2830 or use of sequence or conformational specific antibodies58 are required to clarify the details.…”

Section: Discussionmentioning

confidence: 99%

In vitro membrane protein synthesis inside Sec translocon-reconstituted cell-sized liposomes

Ohta

Kato

Watanabe

et al. 2016

Sci Rep

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Protein synthesis using an in vitro transcription-translation system (IVTT) inside cell-sized liposomes has become a valuable tool to study the properties of biological systems under cell-mimicking conditions. However, previous liposome systems lacked the machinery for membrane protein translocation. Here, we reconstituted the translocon consisting of SecYEG from Escherichia coli inside cell-sized liposomes. The cell-sized liposomes also carry the reconstituted IVTT, thereby providing a cell-mimicking environment for membrane protein synthesis. By using EmrE, a multidrug transporter from E. coli, as a model membrane protein, we found that both the amount and activity of EmrE synthesized inside the liposome is increased approximately three-fold by incorporating the Sec translocon. The topological change of EmrE induced by the translocon was also identified. The membrane integration of 6 out of 9 E. coli inner membrane proteins that was tested was increased by incorporation of the translocon. By introducing the Sec translocon, the membrane integration efficiency of the membrane protein of interest was increased, and enabled the integration of membrane proteins that otherwise cannot be inserted. In addition, this work represents an essential step toward the construction of an artificial cell through a bottom-up approach.

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“…LPSs are initially soluble but over time LPSs typically form large heterogeneous aggregates with molecular masses of 1–4 Mda or greater, and these structures are exceptionally immunogenic to the host [ 61 – 65 ]. Activation via LPS involves interactions with innate immunity-receptors such as Toll-like receptor 4 (TLR4; see below) in complex with MD-2 protein (also known as lymphocyte antigen 96) and accessory proteins, such as the cluster of differentiation innate-immune protein 14 (CD14) and LPS-binding protein [ 19 , 63 , 64 ]. LPS and MD-2 specifically activate the human TLR4 leading to the production of a highly pleiotropic mixture of cytokines and chemokines which in turn promote inflammatory and innate-immune responses [ 61 – 64 ].…”

Section: Secretory Elements Of the Human Microbiomementioning

confidence: 99%

“…Activation via LPS involves interactions with innate immunity-receptors such as Toll-like receptor 4 (TLR4; see below) in complex with MD-2 protein (also known as lymphocyte antigen 96) and accessory proteins, such as the cluster of differentiation innate-immune protein 14 (CD14) and LPS-binding protein [ 19 , 63 , 64 ]. LPS and MD-2 specifically activate the human TLR4 leading to the production of a highly pleiotropic mixture of cytokines and chemokines which in turn promote inflammatory and innate-immune responses [ 61 – 64 ]. Bacterial LPS is considered to possess a prototypical pathogen-associated molecular pattern or PAMP, consisting of LPSs arranged in a highly specific molecular configuration efficiently recognized by host innate-immunity [ 60 , 65 ].…”

Section: Secretory Elements Of the Human Microbiomementioning

confidence: 99%

Microbial Sources of Amyloid and Relevance to Amyloidogenesis and AlzheimerÂ’s Disease (AD)

Zhao

2015

J Alzheimers Dis Parkinsonism

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Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to development, immunity, neurophysiology, metabolic and nutritive support to central nervous system (CNS) health and disease. What is not generally appreciated is that (i) the ~1014 microbial cells that comprise the human microbiome outnumber human host cells by approximately one hundred-to-one; (ii) together the microbial genes of the microbiome outnumber human host genes by about one hundred-and-fifty to one; (iii) collectively these microbes constitute the largest ‘diffuse organ system’ in the human body, more metabolically active than the liver; strongly influencing host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and neurotransmission-functions; and (iv) that these microbes actively secrete highly complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their outer membranes into their immediate environment. While secreted LPS and amyloids are generally quite soluble as monomers over time they form into highly insoluble fibrous protein aggregates that are implicated in the progressive degenerative neuropathology of several common, age-related disorders of the human CNS including Alzheimer’s disease (AD). This general commentary-perspective paper will highlight some recent findings on microbial-derived secreted LPS and amyloids and the potential contribution of these neurotoxic and proinflammatory microbial exudates to age-related inflammatory amyloidogenesis and neurodegeneration, with specific reference to AD wherever possible.

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Lipids and Extracellular Materials

Abstract: This article introduces the Lipids and Extracellular Materials theme of the Annual Review of Biochemistry, Volume 83.

Cited by 9 publications

References 10 publications

Observing a Lipid-Dependent Alteration in Single Lactose Permeases

Observing a Lipid-Dependent Alteration in Single Lactose Permeases

In vitro membrane protein synthesis inside Sec translocon-reconstituted cell-sized liposomes

Microbial Sources of Amyloid and Relevance to Amyloidogenesis and AlzheimerÂ’s Disease (AD)

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