Project description:Cullin-RING ubiquitin ligases (CRLs) control the degradation of a wide landscape of human proteins in combination with ubiquitin-carrying enzymes (UCEs). CRL expansion during evolution is apparent, with a few dozen in yeast that function with a single UCE and as many as 300 in humans that function with at least 8 UCEs. A major unaddressed question is why human CRL buildup has been accompanied by additional UCEs that function with CRLs. Here we demonstrate that human CRLs and UCEs can display specificity, resulting in increased affinity for each other and enhanced rates of ubiquitin transfer to substrates. To uncover the structural basis for CRL-UCE specificity, cryo-EM was performed on a CRL2 subfamily member with substrate receptor subunit FEM1C (CRL2FEM1C) in complex with a proxy for catalytically active UCE. The structure elucidated an extensive CRL-UCE interface that promotes proximity between the UCE active site and CRL2FEM1C-bound substrate. Unanticipated selectivity was also observed between the CRL substrate Lys ubiquitylation sites and the identity of the UCE. CRL-UCE specificity also manifests during targeted protein degradation by affecting the activities of drugs that induce ubiquitylation of neosubstrates. An emerging CRL code is revealed that drives selective formation of CRL-UCE complexes to promote rapid substrate ubiquitylation.
Project description:The manuscript by D. Licastro and colleagues “Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements” presents an overview of experimental and computational approaches employed by the authors to perform a multi-facet characterization of ultraconserved elements (UCEs). The authors present an interesting analysis where they investigate the transcription of UCEs in mouse development at different stages by conductin an microarray experiment. Some of these results are further verified by RT-PCR.
2010-06-16 | GSE19371 | GEO
Project description:Data from targeted capture of conserved squamate loci (SqCL) in the Matuwa, WA lizard community
Project description:The manuscript by D. Licastro and colleagues “Promiscuity of enhancer, coding and non-coding transcription functions in ultraconserved sequence elements” presents an overview of experimental and computational approaches employed by the authors to perform a multi-facet characterization of ultraconserved elements (UCEs). The authors present an interesting analysis where they investigate the transcription of UCEs in mouse development at different stages by conductin an microarray experiment. Some of these results are further verified by RT-PCR. 12 Samples, 4 groups 3 samples per group.
Project description:Metabolically similar cohorts of bacteria exhibit strong cooccurrence patterns with diet items and eukaryotic microbes in lizard guts
