| 1. |
- Bous, J, et al.
(författare)
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Structure of the vasopressin hormone-V2 receptor-β-arrestin1 ternary complex
- 2022
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:35, s. eabo7761-
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Tidskriftsartikel (refereegranskat)abstract
- Arrestins interact with G protein–coupled receptors (GPCRs) to stop G protein activation and to initiate key signaling pathways. Recent structural studies shed light on the molecular mechanisms involved in GPCR-arrestin coupling, but whether this process is conserved among GPCRs is poorly understood. Here, we report the cryo–electron microscopy active structure of the wild-type arginine-vasopressin V2 receptor (V2R) in complex with β-arrestin1. It reveals an atypical position of β-arrestin1 compared to previously described GPCR-arrestin assemblies, associated with an original V2R/β-arrestin1 interface involving all receptor intracellular loops. Phosphorylated sites of the V2R carboxyl terminus are clearly identified and interact extensively with the β-arrestin1 N-lobe, in agreement with structural data obtained with chimeric or synthetic systems. Overall, these findings highlight a notable structural variability among GPCR-arrestin signaling complexes.
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| 2. |
- Gruszczyk, J, et al.
(författare)
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Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 7010-
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Tidskriftsartikel (refereegranskat)abstract
- The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity of structural data precludes understanding of how AHR is activated by such diverse compounds. Our 2.85 Å structure of the human indirubin-bound AHR complex with the chaperone Hsp90 and the co-chaperone XAP2, reported herein, reveals a closed conformation Hsp90 dimer with AHR threaded through its lumen and XAP2 serving as a brace. Importantly, we disclose the long-awaited structure of the AHR PAS-B domain revealing a unique organisation of the ligand-binding pocket and the structural determinants of ligand-binding specificity and promiscuity of the receptor. By providing structural details of the molecular initiating event leading to AHR activation, our study rationalises almost forty years of biochemical data and provides a framework for future mechanistic studies and structure-guided drug design.
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| 3. |
- Lai-Kee-Him, J., et al.
(författare)
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In vitro versus in vivo cellulose microfibrils from plant primary wall synthases : Structural differences
- 2002
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:40, s. 36931-36939
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Tidskriftsartikel (refereegranskat)abstract
- Detergent extracts of microsomal fractions from suspension cultured cells of Rubus fruticosus (blackberry) were tested for their ability to synthesize in vitro sizable quantities of cellulose from UDP-glucose. Both Brij 58 and taurocholate were effective and yielded a substantial percentage of cellulose microfibrils together with (1-->3)-beta-D-glucan (callose). The taurocholate extracts, which did not require the addition of Mg2+, were the most efficient, yielding roughly 20% of cellulose. This cellulose was characterized after callose removal by methylation analysis, electron microscopy, and electron and x-ray synchrotron diffractions; its resistance toward the acid Updegraff reagent was also evaluated. The cellulose microfibrils synthesized in vitro had the same diameter as the endogenous microfibrils isolated from primary cell walls. Both polymers diffracted as cellulose IVI, a disorganized form of cellulose I. Besides these similarities, the in vitro microfibrils had a higher perfection and crystallinity as well as a better resistance toward the Updegraff reagent. These differences can be attributed to the mode of synthesis of the in vitro microfibrils that are able to grow independently in a neighbor-free environment, as opposed to the cellulose in the parent cell walls where new microfibrils have to interweave with the already laid polymers, with the result of a number of structural defects.
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