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The two sides of a lipid-protein story.

ABSTRACT: Protein-membrane interactions play essential roles in a variety of cell functions such as signaling, membrane trafficking, and transport. Membrane-recruited cytosolic proteins that interact transiently and interfacially with lipid bilayers perform several of those functions. Experimental techniques capable of probing changes on the structural dynamics of this weak association are surprisingly limited. Among such techniques, electron spin resonance (ESR) has the enormous advantage of providing valuable local information from both membrane and protein perspectives by using intrinsic paramagnetic probes in metalloproteins or by attaching nitroxide spin labels to proteins and lipids. In this review, we discuss the power of ESR to unravel relevant structural and functional details of lipid-peripheral membrane protein interactions with special emphasis on local changes of specific regions of the protein and/or the lipids. First, we show how ESR can be used to investigate the direct interaction between a protein and a particular lipid, illustrating the case of lipid binding into a hydrophobic pocket of chlorocatechol 1,2-dioxygenase, a non-heme iron enzyme responsible for catabolism of aromatic compounds that are industrially released in the environment. In the second case, we show the effects of GPI-anchored tissue-nonspecific alkaline phosphatase, a protein that plays a crucial role in skeletal mineralization, and on the ordering and dynamics of lipid acyl chains. Then, switching to the protein perspective, we analyze the interaction with model membranes of the brain fatty acid binding protein, the major actor in the reversible binding and transport of hydrophobic ligands such as long-chain, saturated, or unsaturated fatty acids. Finally, we conclude by discussing how both lipid and protein views can be associated to address a common question regarding the molecular mechanism by which dihydroorotate dehydrogenase, an essential enzyme for the de novo synthesis of pyrimidine nucleotides, and how it fishes out membrane-embedded quinones to perform its function.

SUBMITTER: Basso LGM

PROVIDER: S-EPMC5425782 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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The two sides of a lipid-protein story.

Basso Luis G Mansor LGM Mendes Luis F Santos LFS Costa-Filho Antonio J AJ

Biophysical reviews 20160430 2

Protein-membrane interactions play essential roles in a variety of cell functions such as signaling, membrane trafficking, and transport. Membrane-recruited cytosolic proteins that interact transiently and interfacially with lipid bilayers perform several of those functions. Experimental techniques capable of probing changes on the structural dynamics of this weak association are surprisingly limited. Among such techniques, electron spin resonance (ESR) has the enormous advantage of providing va ...[more]

PMID: 28510056

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Project description:OBJECTIVES:Fatigue is a common symptom in primary care. Chronic fatigue research highlights the value of preventing chronicity, but little research has investigated the early, subacute stage of the fatigue trajectory (<3 months). We aimed to examine patient and general practitioner (GP) perspectives of subacute fatigue in primary care: (1) to gain a better understanding of fatigue during this stage and (2) to explore how management could be improved. DESIGN:A qualitative study design was used. In-depth, semi-structured telephone interviews were conducted with 14 patients and 14 GPs (non-dyadic), recruited from 19 primary care practices. METHODS:Interview transcripts were thematically analysed. Initially, patient and GP accounts were analysed separately, before themes were merged to identify shared and independent perspectives. RESULTS:Three main themes were identified. Within these, subthemes from patients', GPs', or shared patient/GP perspectives emerged. The main themes encompassed the following: (1) Change from normal - the impact of fatigue; (2) The challenges of managing fatigue; and (3) The consultation GPs' knowledge was often not reflected in patients' accounts, even for those reporting positive experiences, suggesting knowledge was not effectively translated. CONCLUSIONS:Some findings, such as impact, mirror those described in chronic fatigue. New insights into early-stage fatigue management also arose, including mismatches in patient and GP perceptions on negative tests and not re-presenting. These highlight the need for better communication and shared understanding. GPs should pre-emptively present a biopsychosocial model of fatigue and keep communication channels open, particularly in the light of negative physiological tests. Statement of contribution What is already known on this subject? Patients with chronic fatigue retrospectively report lack of understanding from GPs in early stage of illness. Little research has investigated the early stages of the fatigue trajectory. What does this study add? Consequences of an episode of subacute fatigue are similar to those reported for CFS. There is discordance between GPs' positive view of negative tests and patients' need for explanation of symptoms. The length of appointments is a significant barrier for creating shared understanding.

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The two sides of a lipid-protein story.

Publications

The two sides of a lipid-protein story.

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