Talin as a memory molecule #MeshCODE.
Talin shock absorbing materials #TSAM.
Professor of Mechanistic Cell Biology at University of Liverpool
Dad, Husband. Hobbies: Mechanobiology, talin, looking at the sky
Ben Goult
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Our current thinking is that either additional cellular/mechanical cues regulate this interaction, or that much of the KANK visible in cultured cells is already active.
Either way, there is clearly more biology here to uncover.
New preprint
We identify a conserved intramolecular interaction in KANK proteins.
We show that the KANK KN domain contains separable functional modules: the LD motif mediates talin binding, while residues 60-68 mediate interaction with the KANK ankyrin repeat domain
doi.org/10.64898/202...
Ben Goult
Ben Goult
2/ The structure itself looks remarkably similar to wildtype.
The surprise came from the biochemistry.
A50I disrupts binding to some talin vinculin-binding sites, but retains essentially wildtype affinity for others.
One aspect of the project that surprised us was the contrast between the biochemistry and the cell biology.
The interaction was robust, conserved across the KANK family and easy to detect biochemically. Yet it was remarkably difficult to find a clear cellular consequence of disrupting it.
1/ Our new crystal structure is now available in the PDB (9SR0).
It is the structure of the widely used A50I vinculin mutant bound to talin.
Which is slightly awkward, because A50I is supposed to be a talin-binding-null mutant.
rcsb.org/structure/9SR0
3/ That observation sent us down a much bigger rabbit hole.
We eventually showed that force can unfold talin rod domains and expose vinculin-binding sites that A50I can still bind, leading us to develop a new talin-binding-null mutant and revisit vinculin mechanotransduction.
1/ Our new crystal structure is now available in the PDB (9SR0).
It is the structure of the widely used A50I vinculin mutant bound to talin.
Which is slightly awkward, because A50I is supposed to be a talin-binding-null mutant.
rcsb.org/structure/9SR0
1/ Our new preprint is out today.🎉
It started from a surprising control experiment while studying how talin binds vinculin.
We were using the widely adopted A50I vinculin mutant to disrupt talin binding — but unexpectedly, it still bound talin.
www.biorxiv.org/content/10.6...
All the constructs for working with new improved talin-binding-null mutant of vinculin are now on @addgene.bsky.social www.addgene.org/browse/artic...
Sometimes the most interesting result comes from the control experiment.
PDB: 9SR0
Preprint link www.biorxiv.org/content/10.6...
