ICR researchers have, for the first time, revealed the structure and behaviour of active CDK11, a key protein driving the growth of multiple cancer types and uncovered a new mechanism regulating its activity. More from us here ⤵️

New understanding of enzyme regulating gene expression could inform future cancer therapies

New understanding of enzyme regulating gene expression could inform future cancer therapies

icr.ac.uk

The early release version of our #cryoEM work on CDK11-cyclin L-SAP30BP has now been published at Nature Communications: www.nature.com/articles/s41... We got very helpful comments from the reviewers and added more structural analysis and biochemistry to support our conclusions. Please have a look!

Basil Greber@bjgreber.bsky.social · 6mo ago

Have a look at our latest results on #CDK regulation, just posted as a pre-print! This study was spearheaded by PhD student Amy McGeoch. Amy has determined the #cryoEM structure of the CDK11-cyclin L-SAP30B complex, an important regulator of #spliceosome activation. www.biorxiv.org/content/10.6...

Have a look at our latest results on #CDK regulation, just posted as a pre-print! This study was spearheaded by PhD student Amy McGeoch. Amy has determined the #cryoEM structure of the CDK11-cyclin L-SAP30B complex, an important regulator of #spliceosome activation. www.biorxiv.org/content/10.6...

Now out in Science! Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle. In @vcushing.bsky.social's magnum opus, we use #cryoEM to figure out how the CDK-activating kinase recognises CDKs to fully activate them - a key step in cell cycle control. www.science.org/doi/10.1126/...

Structural basis of T-loop–independent recognition and activation of CDKs by the CDK-activating kinase

Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation o...

science.org

New paper out now in Science! Check it out! www.science.org/doi/10.1126/...

Structural basis of T-loop–independent recognition and activation of CDKs by the CDK-activating kinase

Cyclin-dependent kinases (CDKs) are prototypical regulators of the cell cycle. The CDK-activating kinase (CAK) acts as a master regulator of CDK activity by catalyzing the activating phosphorylation o...

science.org

Resistance to CDK7 inhibitors directed by acquired mutation of a conserved residue in cancer cells Laki Buluwela @simak.bsky.social @bjgreber.bsky.social et al find a single base change of #CDK7 conferring resistance to non-covalent CDK inhibition in prostate cancer www.embopress.org/doi/full/10....

We show a single amino acid change in CDK7 causes acquired resistance to CDK7i in cancer cells. There are implications for patient selection,resistance monitoring and switching treatments. thanks to @vcushing.bsky.social @bjgreber.bsky.social @prostatecanceruk.bsky.social doi.org/10.1038/s443...

Just published: Our paper on high-throughput analysis of cyclin docking interactions, led by the group of Norman Davey @icr.ac.uk and with some small-complex-plus-peptide #cryoEM by @natalia-mg.bsky.social from my lab. Congratulations, everyone! www.nature.com/articles/s41...

High-throughput investigation of cyclin docking interactions reveals the complexity of motif binding determinants - Nature Communications

Many protein–protein interactions depend on Short Linear Motifs (SLiMs). In this study, the authors use large-scale binding assays, deep mutational scanning, and structural analysis to map SLiMs recog...

nature.com

Now out in Structure: Paper on high-resolution #cryoEM using the 100 kV Tundra cryo-TEM by Dimple Karia, Adrian Koh, @abhaykot.bsky.social, @lingboyu.bsky.social, @landerlab.bsky.social and many others. Happy to have contributed to this effort. Check it out: www.sciencedirect.com/science/arti...

Sub-3 Å resolution protein structure determination by single-particle cryo-EM at 100 keV

Cryoelectron microscopy (cryo-EM) has transformed structural biology by providing high-resolution insights into biological macromolecules. We report s…

sciencedirect.com

For our latest paper, we worked with SYROS Pharmaceuticals, the groups of Dylan Taatjes and Robin Dowell at CU Boulder, and @abhaykot.bsky.social. Junjie Feng in my lab determined the #cryoEM structure of the CDK7 inhibitor SY5609 bound to its target... www.science.org/doi/10.1126/...

TFIIH kinase CDK7 drives cell proliferation through a common core transcription factor network

CDK7 kinase activity is found to control RNAPII transcription through a cohort of TFs that drive cell cycle and proliferation.

science.org

New pre-print! To support a CDK-cyclin docking motif discovery and characterisation project led by Norman Davey and colleagues, @natalia-mg.bsky.social in my lab determined the #cryoEM structures of three peptide-bound CDK2-cyclin A complexes. Check it out! www.biorxiv.org/content/10.1...

High-throughput discovery and deep characterization of cyclin-CDK docking motifs

Cyclin-CDKs are master regulators of cell division. In addition to directly activating the CDK, the cyclin subunit regulates CDK specificity by binding short peptide “docking” motifs in CDK substrates...

biorxiv.org