Dataset Information

In silico identification of lipid-binding ? helices of uncoupling protein 1.

ABSTRACT: Uncoupling protein 1 (UCP1) located at the mitochondrial inner membrane serves an important role in adaptive non-shivering thermogenesis. Previous data has demonstrated that membrane lipids regulate the biological functions of membrane proteins. However, how mitochondrial lipids interact with UCP1 still remains elusive. In this study, the interactions between UCP1 and membrane lipids were investigated, using bioinformatic approaches due to the limitations associated with experimental techniques. A total of 8 UCP1 peptide regions with ?-helices were identified and related to functional sites of UCP1. These were all novel peptide sequences compared with the known protein-lipid interactions. Among several types of UCP1-binding molecules, cardiolipin appeared to serve as a key interacting molecule of the 8 lipid-binding ?-helix regions of UCP1. Two cardiolipin-binding lysines (K175 and K269) of UCP1 may be crucial for this UCP1-cardiolipin recognition and UCP1 function. The present findings provide novel insight into the associations of UCP1 with lipids and the potential drug targets in UCP1-associated diseases.

SUBMITTER: Jing Y

PROVIDER: S-EPMC6142039 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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<i>In silico</i> identification of lipid-binding α helices of uncoupling protein 1.

Jing Ying Y Niu Yahan Y Liu Chang C Zen Ke K Li Donghai D

Biomedical reports 20180723 4

Uncoupling protein 1 (UCP1) located at the mitochondrial inner membrane serves an important role in adaptive non-shivering thermogenesis. Previous data has demonstrated that membrane lipids regulate the biological functions of membrane proteins. However, how mitochondrial lipids interact with UCP1 still remains elusive. In this study, the interactions between UCP1 and membrane lipids were investigated, using bioinformatic approaches due to the limitations associated with experimental techniques. ...[more]

PMID: 30233783

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Project description:Tau is a microtubule-associated protein that is genetically linked to dementia and linked to Alzheimer's disease via its presence in intraneuronal neurofibrillary tangle deposits, where it takes the form of aggregated paired helical and straight filaments. Although the precise mechanisms by which tau contributes to neurodegeneration remain unclear, tau aggregation is commonly considered to be a critical component of tau-mediated pathogenicity. Nevertheless, the context in which tau aggregation begins in vivo is unknown. Tau is enriched in membrane-rich neuronal structures such as axons and growth cones, and can interact with membranes both via intermediary proteins and directly via its microtubule-binding domain (MBD). Membranes efficiently facilitate tau aggregation in vitro, and may therefore provide a physiologically relevant context for nucleating tau aggregation in vivo. Furthermore, tau-membrane interactions may potentially play a role in tau's poorly understood normal physiological functions. Despite the potential importance of direct tau-membrane interactions for tau pathology and physiology, the structural mechanisms that underlie such interactions remain to be elucidated. Here, we employ electron spin resonance spectroscopy to investigate the secondary and long-range structural properties of the MBD of three-repeat tau isoforms when bound to lipid vesicles and membrane mimetics. We show that the membrane interactions of the tau MBD are mediated by short amphipathic helices formed within each of the MBD repeats in the membrane-bound state. To our knowledge, this is the first detailed elucidation of helical tau structure in the context of intact lipid bilayers. We further show, for the first time (to our knowledge), that these individual helical regions behave as independent membrane-binding sites linked by flexible connecting regions. These results represent the first (to our knowledge) detailed structural view of membrane-bound tau and provide insights into potential mechanisms for membrane-mediated tau aggregation. Furthermore, the results may have implications for the structural basis of tau-microtubule interactions and microtubule-mediated tau aggregation.

Dataset Information

In silico identification of lipid-binding ? helices of uncoupling protein 1.

Publications

<i>In silico</i> identification of lipid-binding α helices of uncoupling protein 1.

Similar Datasets

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