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Targeted protein degradation via intramolecular bivalent glues

Targeted protein degradation is a pharmacological modality that is based on the induced proximity of an E3 ubiquitin ligase and a target protein to promote target ubiquitination and proteasomal degradation. This has been achieved either via proteolysis-targeting chimeras (PROTACs)—bifunctional compounds composed of two separate moieties that individually bind the target and E3 ligase, or via molecular glues that monovalently bind either the ligase or the target1–4. Here, using orthogonal genetic screening, biophysical characterization and structural reconstitution, we investigate the mechanism of action of bifunctional degraders of BRD2 and BRD4, termed intramolecular bivalent glues (IBGs), and find that instead of connecting target and ligase in trans as PROTACs do, they simultaneously engage and connect two adjacent domains of the target protein in cis. This conformational change ‘glues’ BRD4 to the E3 ligases DCAF11 or DCAF16, leveraging intrinsic target̵ ....

South Korea , Van Molle , Acta Crystallogr , Development Of Bromotag , Drug Discovery , Nucleic Acids Res , Acids Res , Graphics System ,

Vaccination with Span, an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice

Vaccination with Span, an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

United States , South Africa , Pulser Xcell , Research Of Wuhan University , Frontier Research Program Of The Wuhan Government , Innovation Team Research Program Of Hubei Province , Gempharmatech Co , Research Funds For The Central Universities , Zhubei Center , Graphpad Software Inc , National Center , National Natural Science Foundation Of China , Wuhan Institute Of Biological Products Co , World Health Organization , Wuhan University , Taikang Yicai Foundation , Global Initiative On Sharing All Influenza Data , Protein Data Bank , Yan Wuhan University , Wuhan Servicebio Technology Co , Xia Xiamen University , Animal Committee Of Wuhan University , National Institute Of Biological Science , Complex Heatmap , Global Initiative , Sharing All Influenza Data ,

The first Apple Tablet… from 1979 | Edible Apple

The first Apple Tablet… from 1979 | Edible Apple
edibleapple.com - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from edibleapple.com Daily Mail and Mail on Sunday newspapers.

Tod Rundgren , Graphics Tablet , Apple Graphics Tablet , Graphics System , Utopia Graphics Tablet System , Utopia Graphics Tablet , Snow Leopard ,

Class I histone deacetylases (HDAC1–3) are histone lysine delactylases

Class I histone deacetylases (HDAC1–3) are histone lysine delactylases
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

United States , University Of Chicago , Millipore Temecula , Fluorogenic Michaelis Menten , Milliporesigma Burlington , Cell Signaling Technology Inc , Ge Healthcare Life Sciences , Research Fund Denmark , Enzo Life Sciences , Abclonal Inc , Ge Healthcare , Ministry Of Science , Production Sciences , Cayman Chemical Company , Biolabs Inc , Natural Sciences , Olsen Lab , Carlsberg Foundation , Danish Council For Independent Research , Maponos Therapeutics Inc , Fisher Scientific , European Research Council , Santa Cruz Biotechnology Inc , Macherey Nagel Gmbh Co , Technology Of China , Supplementary Methods ,

Neuroserpin and transthyretin are extracellular chaperones that preferentially inhibit amyloid formation

Neuroserpin and transthyretin are extracellular chaperones that preferentially inhibit amyloid formation
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

United States , South Australia , New South Wales , United Kingdom , Baden Wüberg , Switzerland General , Genscript Piscataway , Polarstar Omega , Dako Agilent , Actilyse Boehringer Ingelheim , Royal Society , Research Collaboratory , Protein Production Unit Monash University , Centre For Misfolding Diseases United Kingdom , Structural Bioinformatics Protein Data Bank , Atmospheric Life Sciences , Graphpad Software , University Research Fellowship , P Curmi University Of New South Wales , Ge Healthcare , National Center , School Of Earth , University Of Wollongong , Australian Research Council , Pall Life Sciences , Research Institute ,