Pint of Science was again a great success in Lausanne, with >500 people attending our events!
Kudos to co-coordinators @miriamlisci.bsky.social and @juliensluneau.bsky.social, and to the fantastic team of 19 volunteers at the bars 🥳!

#PINT25 #scicomm

This would not have been possible without the excellent (and very efficient!) contributions of Babatunde Ekundayo and Polina Foteva (who just defended her MSc thesis 🥳), of Dongchun Ni, Esther Calviño and Henning Stahlberg, or without the truly supportive guidance of @beatfierz.bsky.social.
(7/8)

The contacts of the catalytic domain with DNA, on the other hand, are responsible for maintaining #H3K36ac selectivity.
Mutating a key interacting loop helps release the enzyme from the nucleosome and become much more active on #H3K18ac substrates 🤯.
(6/8)

The multivalent interactions of the nucleosome-binding domain are important for both activities, especially to find #chromatin substrates in an environment full of nucleic acids.
Interestingly, this domain is only present in insects and most vertebrates.
(5/8)

By comparing structures trapped at each substrate position we could rationalize its activity and intrinsic selectivity 🔍.
#SIRT7 binding is optimal for targeting #H3K36ac, and it can only access #H3K18ac through partial disengagement from the nucleosome and DNA bending.
(4/8)

Babatunde Ekundayo generated beautiful high-resolution structures, where we identified:
- A unique N-terminal nucleosome-binding domain, which places the #SIRT7 catalytic domain by the H3 tail exit site
- Extensive contacts with the two DNA gyres!
(3/8)

We produced nucleosomes with a thiourea mechanism-based handle (MTU) at the H3K18 and H3K36 preferred substrate positions, through histone semi-synthesis and reconstitution in vitro.
This allowed us to stabilize specific enzyme:substrate complexes efficiently for #cryoEM.
(2/8)

#SIRT7 is a histone deacetylase with highly specific activity on #chromatin substrates.
We just published mechanism-based #cryoEM structures of #SIRT7 on nucleosomes to understand its activity 👇
www.nature.com/articles/s41...
(1/8) #ChemBio #ChemSky