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MRC Laboratory of Molecular Biology

MRC Laboratory of Molecular Biology

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Repeating peptides are obstacles to neuronal transport in motor neurone disease

Cartoon showing model for how motor neurone disease-associated peptides impair movement of a key microtubule motor.

Repetitive peptides from the C9orf72 gene contribute to the most prevalent form of motor neurone disease, but it has been unclear how. Simon Bullock’s group help show how these peptides bind to both motor proteins and microtubule tracks to block neuronal transport.

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Published on 19th April, 2021

How timing in early brain development sets humans apart from apes

Human and ape neural progenitors

The advent of brain organoid technology has enabled scientists to begin to ask what makes us human. Madeline Lancaster’s group has identified differences in early brain development that can help to explain the increased number of neurons in human brains over other apes.

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Published on 24th March, 2021

Capturing the activation of a lipid kinase on membranes by G-proteins

Electron cryo-tomography of VPS34 complex II bound to Rab5 on lipid vesicles, shows a range of orientations of the complex relative to the membrane, which allows the activated VPS34 kinase to survey the vesicle for substrate.

Rare lipids in our cell membranes act as postcodes to operate regulatory processes such as autophagy and endocytosis. Roger Williams, together with Sean Munro’s and John Brigg’s groups, have shown how the G-proteins Rab1 and Rab5 activate these processes respectively, through conformational changes of kinase VPS34 complexes.

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Published on 10th March, 2021

Understanding TRIM21 activation allows Trim-Away toolbox expansion

Trim-Away technology allows rapid destruction of cellular proteins

A powerful strategy to study protein function has been to deplete a protein of interest from the cell and then study the consequences. Leo James’ group has exploited new understanding of TRIM21’s mechanism of activation to develop new tools for targeted protein degradation.

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Published on 9th March, 2021

Following protein footprints on RNA to track splicing fidelity

A structural snapshot of a post-catalytic spliceosome bound to mRNA with the psiCLIP binding profile for the ATPase Prp22 mapped onto it. Prp22 is poised to pull from a defined region on the bound mRNA to release it from the spliceosome.

Studying splicing fidelity has been difficult as some of the factors known to promote correct splice site use bind the spliceosome only transiently. Kiyoshi Nagai’s group have developed a method to study how proteins that ensure fidelity bind to RNA at different stages of splicing.

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Published on 5th March, 2021

TRIM21 is both enzyme and substrate when creating a signal to degrade bound viruses and proteins

An Adenovirus capsid, bound by TRIM21-antibody complexes. This allows TRIM21 to localize 3 of its RING E3 ligase domains in close proximity, allowing self-ubiquitination. The zoom shows the crystal structure capturing this process.

The intracellular immune receptor TRIM21 detects antibody-bound viruses inside our cells and targets them for destruction by creation of a polyubiquitin signal. David Neuhaus’ group, with Leo James’, has shown that TRIM21 is both the enzyme and recipient of the ubiquitination.

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Published on 2nd March, 2021
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