Characterisation of the ligand binding sites in the translocator protein TSPO using the chimeric bacterial-mammalian constructs

Publication date: December 2019Source: Protein Expression and Purification, Volume 164Author(s): Elisabeth Graeber, Volodymyr M. KorkhovAbstractThe translocator protein TSPO is in an important diagnostic and therapeutic target in a range of pathologies, including neuroinflammation and cancer. Despite the availability of several structures of TSPO homologues, our understanding of the molecular determinants that govern high-affinity interactions of TSPO with its ligands is incomplete. Here, in order to decipher the key structural elements of TSPO responsible for interactions with its ligands, we designed a panel of chimeric proteins mimicking the mammalian substrate binding site grafted onto the backbone of the Rhodobacter sphaeroides TSPO homologue, RsTSPO. One of the designed chimeric constructs, RsMouse, could be heterologously expressed and displayed improved binding affinities for the known TSPO drugs diazepam, PK11195 and NBD-FGIN-1-27. Furthermore, the chimeric protein had improved interactions with NBD-cholesterol, a fluorescent analogue of the presumed natural substrate of TSPO. Partial modifications of the transmembrane helix bundle in the chimeric construct differentially affected binding of the TSPO drugs and the natural substrates of TSPO, consistent with the presence of multiple ligand binding sites in the protein. Based on the available structures of TSPO homologues, the substrate interactions may involve a lateral opening of the protein in the TM1-3, and stabili...
Source: Protein Expression and Purification - Category: Biochemistry Source Type: research

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Expression of LXR‑β, ABCA1 and ABCG1 in human triple‑negative breast cancer tissues. Oncol Rep. 2019 Aug 14;: Authors: Pan H, Zheng Y, Pan Q, Chen H, Chen F, Wu J, Di D Abstract Previous studies have reported that liver X receptor (LXR), ATP‑binding cassette sub‑family G number 1 (ABCG1) and ATP‑binding cassette transporter number 1 (ABCA1), which are associated with cholesterol metabolism, may be associated with the development and progression of breast cancer. The expression levels of LXR‑β, ABCA1 and ABCG1 in triple‑negative breast cancer (TNBC) tissues and in non‑canc...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
SREBP2 is upregulated in esophageal squamous cell carcinoma and co‑operates with c‑Myc to regulate HMGCR expression. Mol Med Rep. 2019 Aug 09;: Authors: Zhong C, Fan L, Li Z, Yao F, Zhao H Abstract Dysregulations of the mevalonate pathway (MVA) have been previously identified. Our previous study demonstrated that 3‑hydroxy‑3‑methylglutaryl‑coenzyme A reductase (HMGCR), the rate‑limiting enzyme of the MVA pathway, was upregulated in esophageal squamous cell carcinoma (ESCC) and statin‑inhibited ESCC tumorigenesis. However, the underlying mechanism of HMGCR regulation in ESCC remains...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Abstract The anticarcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to 'stage migration', with users more likely diagnosed with early rather than late stage cancer. The association between prior statin use and colorectal cancer (CRC) stage at diagnosis in the Women's Health Initiative (WHI) was investigated. The study population included 132,322 post-menopausal women, among which there were 2,628 pathologically confirmed cases of in situ (3.3%), localized (43.6%), regional (40.4%) and distant (12.7%) stage CRC, after an average of 13.9 (SD=4.7) years of follow-up. To reduce ...
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: Mol Clin Oncol Source Type: research
You're reading Discover Amazing Health Benefits of Apples, originally posted on Pick the Brain | Motivation and Self Improvement. If you're enjoying this, please visit our site for more inspirational articles. An apple a day keeps a doctor away was not coined in vain. Apples seem to have taken a back seat with plenty of other “healthy fruits” hogging the limelight. However, never underestimate the power of apples. Coming in bright colors like green and deep red, these fruits look delightfully amazing. Their juicy sweet flavor can stimulate and tease your taste buds like no other. Apart from this, apples hav...
Source: PickTheBrain | Motivation and Self Improvement - Category: Consumer Health News Authors: Tags: featured health and fitness Benefits of Apples health benefits Health Benefits of Apples Source Type: blogs
But lower rectal cancer risk, suggesting differences in microbiome activity along the length of the bowel, say researchers Related items fromOnMedica Cetuximab with chemo shrinks more secondaries Statins might not cut colorectal cancer risk after all Invest in workforce to roll out bowel cancer screening, urges former health secretary Bowel cancer screening tests exceed target set in Scotland FOB associated with rise in all-cause mortality
Source: OnMedica Latest News - Category: UK Health Source Type: news
AbstractBackgroundFunctional limitations may be more common in middle-aged adults than previously recognized. However, there are few published data on the prevalence of activity limitations, and their association with multimorbidity, among adults 50 to 64  years old.ObjectiveTo describe the prevalence of activity limitations and the association with multimorbidity in middle-aged adults.DesignCross-sectional analysis of US population-based National Health and Nutrition Examination Survey (NHANES) 2011 –2016.ParticipantsThe total number of community-dwelling NHANES participants aged 50 –64 years old is ...
Source: Journal of General Internal Medicine - Category: Internal Medicine Source Type: research
Publication date: Available online 16 July 2019Source: Reproductive ToxicologyAuthor(s): Barbara A. Cohn, Michele A. La Merrill, Nickilou Y. Krigbaum, Miaomiao Wang, June-Soo Park, Myrto Petreas, Gregory Yeh, Russell C. Hovey, Lauren Zimmermann, Piera M. CirilloAbstractWe tested the hypothesis that maternal perinatal serum levels of poly and perfluoroalkyl substances (PFASs) predict risk for breast cancer in daughters in a 54-year follow-up of 9300 daughters born 1959–1967 in the Child Health and Development Studies pregnancy cohort. Total cholesterol and PFASs were measured in archived maternal perinatal serum for 1...
Source: Reproductive Toxicology - Category: Toxicology Source Type: research
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Source: The Doctors Lounge - Oncology - Category: Cancer & Oncology Tags: Gastroenterology, Infections, Internal Medicine, Oncology, Pharmacy, Journal, Source Type: news
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Rheumatoid arthritis (RA) is a progressive, destructive autoimmune arthritis. Break of tolerance and formation of autoantibodies occur years before arthritis. Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) play a crucial role in shaping the immune response and maintaining peripheral tolerance. Here we performed the first epigenomic characterization of LNSCs during health and early RA, by analyzing their transcriptome and DNA methylome in LNSCs isolated from lymph node needle biopsies obtained from healthy controls (HC), autoantibody positive RA-risk individuals and patients with es...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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