Guillaume Gaullier
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guillawme.fediscience.org.ap.brid.gy
Guillaume Gaullier
@guillawme.fediscience.org.ap.brid.gy
96 followers 0 following 110 posts
Researcher from 🇫🇷 doing #cryoEM ❄️🔬 at Uppsala University 🇸🇪
Working on cyanobacterial carboxysomes 🦠, still interested in nucleosome 🧬🙃🧬
Mostly […]

🌉 bridged from ⁂ https://fediscience.org/@Guillawme, follow @ap.brid.gy to interact
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guillawme.fediscience.org.ap.brid.gy
A closer look at this helix indicates that it is rich in basic residues: Lys and Arg account for 34% of its sequence composition. This already suggests that its function is to interact with DNA. Looking at sequence conservation, it seems like the basic […]

[Original post on fediscience.org]
Figure 6. The super-groove recognition helix of ALC1. (a) View of the minor super-groove at SHL 3.5/-5.5, with the basic residues of the SGRH shown as sticks, and the residue numbers at the start and end of the helix indicated. The color code is the same as in Figure 5. The rest of ALC1 and the nucleosome are translucent for clarity. (b) View of the SGRH looking down the helical axis, with the SGRH colored by conservation. (c) Multiple sequence alignment of ALC1 orthologues verified by structure predictions to have a similar domain architecture as human ALC1, including a putative SGRH.
January 2, 2026 at 1:27 PM
guillawme.fediscience.org.ap.brid.gy
So what does this new structure look like?

ALC1 is loosely bound to the #nucleosome, in a conformation that likely doesn't allow it to slide the nucleosome along the DNA, since the two ATPase lobes are not clamping the DNA. But we finally see the macro […]

[Original post on fediscience.org]
Figure 5. Structure of an activation intermediate of ALC1 loosely bound to a PARylated nucleosome. (a) Cryo-EM map colored by chain assignment, following the color codes from Figure 1a for the nucleosome and Figure 2a for ALC1. (b) Atomic model, shown in the same orientations and with the same color code as the map shown in panel (a). (c) Structure of the auto-inhibited state. The antibody used for crystallization is shown as a translucent grey surface. From PDB 7EPU. (d) Structure of the intermediate state (dyad view). From this study. (e) Structure of the active state. From PDB 8B0A. In panels (c), (d) and (e), the ATPase residues mutated in the study by (Lehmann et al., 2017) are shown as spheres. In panels (c) and (d), the macro domain residues R857 and R860, found mutated in cancer, are shown as spheres and labeled, and the ADPr-binding pocket of the macro domain is indicated by an ADPr molecule (shown as balls-and-sticks) modeled by structural superimposition of the structure of the Af1521/ADPr complex from PDB 2BFQ (the Af1521 protein is not shown for clarity). In panels (b), (d) and (e), the nucleosome is shown as a translucent surface for clarity.
January 2, 2026 at 1:26 PM
guillawme.fediscience.org.ap.brid.gy
And here is @HRBridges magic explained in a flow chart. ✨

For more info, consult the preprint's methods section and the case study in the CryoSPARC Guide. This is a compact view of the process, showing what worked best. The map we deposited had job number J8039! 😵‍💫

3/5
Figure 3. Flow chart of the image processing workflow. The steps of each distinct stage are highlighted in different colors: pre-processing in purple, particle picking and curation in blue, consensus reconstruction in green, classification of the complexes with tightly bound ALC1 in yellow, classification of the complexes with loosely bound ALC1 in red, and final refinement of the complex with loosely bound ALC1 in pink. For all steps with a circled number, key visuals are presented in Figure 4, and details are provided in section 6.1 Cryo-EM data processing. Figure 4. Visuals of the key processing steps from Figure 3. The background follows the same color code as in Figure 3. The numbers in parentheses refer to the circled numbers in Figure 3, and details about these are provided in section 6.1 Cryo-EM data processing.
January 2, 2026 at 1:24 PM
guillawme.fediscience.org.ap.brid.gy
In 2021, I was involved in a study of the #chromatin remodeler ALC1, a protein involved in the early events of the DNA damage response. This led to a paper summarized in a previous thread: https://fediscience.org/@Guillawme/111534984107819771

We had deposited the raw #CryoEM data to #empiar […]
Original post on fediscience.org
fediscience.org
January 2, 2026 at 1:18 PM
guillawme.fediscience.org.ap.brid.gy
As promised, here is a summary of this new preprint on the ALC1-nucleosome complex. 🧵

https://doi.org/10.1101/2025.11.10.687450

First, a reminder of some structural features of the #nucleosome.

Histones H2A and H2B form a negatively charged cleft exposed […]

[Original post on fediscience.org]
Figure 1. Structure of the nucleosome. (a) Overview of the nucleosome (disc view). H3 is colored in blue, H4 in green, H2A in yellow, H2B in red, and DNA in grey. From PDB 1AOI. (b) Super-helical locations (SHL) are defined as the points where the major groove faces inward, toward the histone octamer. The base pair at the center of the histone octamer footprint on the DNA is called the dyad and numbered bp 0 / SHL 0 by convention. Each gyre has 7 SHLs, numbered positively on the front gyre and negatively on the back gyre (SHLs with same numbers but opposite signs refer to equivalent locations related by the pseudo 2-fold symmetry of the dyad axis, and a fractional SHL like 1.5 refers to the minor groove between two SHLs, in this example between SHLs 1 and 2). Only the front gyre is displayed here for clarity. From PDB 1AOI. (c) Electrostatic potential of the histone octamer. The H2A-H2B acidic patch is labeled. From PDB 1AOI. (d) The nucleosome’s major and minor super-grooves (gyres view). One of the major super-grooves is indicated by a continuous line (SHL 4/-5). One of the minor super-grooves is indicated by a dashed line (SHL 4.5/-4.5). Super-grooves can be unambiguously referred to by a pair of positive and negative SHLs. The synthetic minor super-groove binder is shown as white spheres. The nucleosome is shown as a surface with the same color code as in panel (a), with the DNA backbone in darker grey. From PDB 1S32.
January 2, 2026 at 1:17 PM
Reposted by Guillaume Gaullier
gedankenstuecke.scholar.social.ap.brid.gy
Instead of a Mozilla fuck-up drinking game: Donate to @servo every time Mozilla gives its community another middle finger. 😁
December 16, 2025 at 3:00 PM
Reposted by Guillaume Gaullier
mastodon.mastodon.social.ap.brid.gy
Today we are calling on institutions around the world to take control of their #digitalsovereignty, including their social accounts. Governments should communicate directly with their citizens on open platforms, not through the mouthpiece of a corporation […]
Original post on mastodon.social
mastodon.social
December 9, 2025 at 11:07 AM
guillawme.fediscience.org.ap.brid.gy
More steps towards a saner model of academic publishing and evaluation:

1. We should all roll with initiatives such as the one linked in the previous post: submit our papers only to society journals and accept to review only for society journals. And preprint everything, of course.

2. We […]
Original post on fediscience.org
fediscience.org
December 5, 2025 at 7:39 AM