Dominik Hrebik
@dhrebik.bsky.social
Postdoc @JohnBriggsGroup @MaxPlanck Institute of Biochemistry in Martinsried
| PhD from PlevkaLab | #StructuralBiology of #Viruses #HIV | #CryoEM | #Memes
Twitter/X: @F4ustus
| PhD from PlevkaLab | #StructuralBiology of #Viruses #HIV | #CryoEM | #Memes
Twitter/X: @F4ustus
This comic is becoming increasingly realistic.
m.xkcd.com/3056/
m.xkcd.com/3056/
September 29, 2025 at 10:50 AM
This comic is becoming increasingly realistic.
m.xkcd.com/3056/
m.xkcd.com/3056/
Proteins are just errands for RNA anyway.
m.xkcd.com/3056/
m.xkcd.com/3056/
March 4, 2025 at 10:39 AM
Proteins are just errands for RNA anyway.
m.xkcd.com/3056/
m.xkcd.com/3056/
Now it was clear that the mysterious ligand density is the conserved SP2 peptide with previously unknown function. The structure revealed that SP2 provides contacts between two neighbouring matrix trimers stabilizing the matrix lattice. 5/5
March 3, 2025 at 6:57 PM
Now it was clear that the mysterious ligand density is the conserved SP2 peptide with previously unknown function. The structure revealed that SP2 provides contacts between two neighbouring matrix trimers stabilizing the matrix lattice. 5/5
To show that SP2 binds and triggers MA maturation in vitro, we used a classic cryoEM method – 2D crystallography on a lipid monolayer. The addition of SP2 triggered the MA+SP2 2D crystal formation and an additional density appeared in the SP2 binding site (dotted square). 4/5
March 3, 2025 at 6:57 PM
To show that SP2 binds and triggers MA maturation in vitro, we used a classic cryoEM method – 2D crystallography on a lipid monolayer. The addition of SP2 triggered the MA+SP2 2D crystal formation and an additional density appeared in the SP2 binding site (dotted square). 4/5
ModelAngelo from @sjorsscheres.bsky.social and @kjamali.bsky.social predicted that the side density is the C-term of the 16 AA long spacer peptide 2 (SP2) from HIV. Together with our experiments on Gag cleavage mutants, this was an indicator that the density is not a lipid but a peptide. 3/5.
March 3, 2025 at 6:57 PM
ModelAngelo from @sjorsscheres.bsky.social and @kjamali.bsky.social predicted that the side density is the C-term of the 16 AA long spacer peptide 2 (SP2) from HIV. Together with our experiments on Gag cleavage mutants, this was an indicator that the density is not a lipid but a peptide. 3/5.
With James Stacey we solved the structure of the HIV-1 matrix protein by SPA to the resolution of 3.1 Å directly from the HIV-1 virions. The map revealed a clear ligand density (orange) in the previously described lipid binding pocket. However, no lipid fit the density. 2/5
March 3, 2025 at 6:57 PM
With James Stacey we solved the structure of the HIV-1 matrix protein by SPA to the resolution of 3.1 Å directly from the HIV-1 virions. The map revealed a clear ligand density (orange) in the previously described lipid binding pocket. However, no lipid fit the density. 2/5
I am very happy to announce that we solved the in-virus #cryoEM structure of the #HIV matrix protein. The structure helped us to resolve a long mystery in HIV biology. A🧵1/5
Read more in Nature: www.nature.com/articles/s41... 🧪
Read more in Nature: www.nature.com/articles/s41... 🧪
March 3, 2025 at 6:57 PM
I am very happy to announce that we solved the in-virus #cryoEM structure of the #HIV matrix protein. The structure helped us to resolve a long mystery in HIV biology. A🧵1/5
Read more in Nature: www.nature.com/articles/s41... 🧪
Read more in Nature: www.nature.com/articles/s41... 🧪
December 2, 2024 at 5:11 PM
November 23, 2024 at 3:18 PM
November 19, 2024 at 5:00 PM
November 15, 2024 at 7:34 PM
The result was striking, only with free SP2 the fusion time was comparable to the mature infectious particle. Whenever SP2 cleavage was defective the particle fused as immature non-infectious particle. 13/x
November 12, 2024 at 9:04 PM
The result was striking, only with free SP2 the fusion time was comparable to the mature infectious particle. Whenever SP2 cleavage was defective the particle fused as immature non-infectious particle. 13/x
To show that SP2 triggers MA maturation in vitro, we used a classic cryo-EM method – 2D crystallography on a lipid monolayer. We discovered that upon the addition of SP2, the grid is covered by an MA+SP2 2D crystal and there is an additional density in the SP2 binding site. 10/x
November 12, 2024 at 9:04 PM
To show that SP2 triggers MA maturation in vitro, we used a classic cryo-EM method – 2D crystallography on a lipid monolayer. We discovered that upon the addition of SP2, the grid is covered by an MA+SP2 2D crystal and there is an additional density in the SP2 binding site. 10/x
ModelAngelo from @sjorsscheres.bsky.social and @kjamali.bsky.social predicted that the side density is the C-terminal part of the 16 AA long spacer peptide 2 (SP2). We could resolve the last 6 amino acids of SP2 forming a salt bridge between two MA molecules triggering MA maturation. 9/x
November 12, 2024 at 9:04 PM
ModelAngelo from @sjorsscheres.bsky.social and @kjamali.bsky.social predicted that the side density is the C-terminal part of the 16 AA long spacer peptide 2 (SP2). We could resolve the last 6 amino acids of SP2 forming a salt bridge between two MA molecules triggering MA maturation. 9/x
In the meantime, we analyzed MA from “HIV-1 Gag cleavage mutant” virions. One can block the protease recognition site in Gag by mutation. We speculated that one of the cleavage sites is an MA maturation trigger. Surprisingly, the common denominator for the mature matrix was a free SP2 peptide! 8/x
November 12, 2024 at 9:04 PM
In the meantime, we analyzed MA from “HIV-1 Gag cleavage mutant” virions. One can block the protease recognition site in Gag by mutation. We speculated that one of the cleavage sites is an MA maturation trigger. Surprisingly, the common denominator for the mature matrix was a free SP2 peptide! 8/x
When we built the atomic model we tried to fit the PIP2 lipid into the density of the binding site. However, neither PIP2 nor any other lipid fit into the density. 7/x
November 12, 2024 at 9:04 PM
When we built the atomic model we tried to fit the PIP2 lipid into the density of the binding site. However, neither PIP2 nor any other lipid fit into the density. 7/x
We trained a crYOLO model that can recognise the features of an HIV-1 virion and oversample the virus surface. Then, we used the known matrix structure from tomography to initialise the reconstruction and classification. 6/x
November 12, 2024 at 9:04 PM
We trained a crYOLO model that can recognise the features of an HIV-1 virion and oversample the virus surface. Then, we used the known matrix structure from tomography to initialise the reconstruction and classification. 6/x
In our study, we decided to follow up on the results of Kun et al. and reveal the role of the matrix in the HIV-1 maturation process. To do so, we first solved the structure of the mature matrix to 3.1 Å directly from the HIV-1 virions by single particle analysis. How did we do it? 4/x
November 12, 2024 at 9:04 PM
In our study, we decided to follow up on the results of Kun et al. and reveal the role of the matrix in the HIV-1 maturation process. To do so, we first solved the structure of the mature matrix to 3.1 Å directly from the HIV-1 virions by single particle analysis. How did we do it? 4/x
It was, however, only in 2021 when my colleague Kun Qu obtained the first in virus structure of the matrix protein (K Qu, Science 2021). It revealed that the matrix undergoes structural rearrangement and binds a ligand upon maturation, which was predicted to be a PIP2 lipid. 3/x
November 12, 2024 at 9:04 PM
It was, however, only in 2021 when my colleague Kun Qu obtained the first in virus structure of the matrix protein (K Qu, Science 2021). It revealed that the matrix undergoes structural rearrangement and binds a ligand upon maturation, which was predicted to be a PIP2 lipid. 3/x
HIV-1 buds from the host cell as a non-infectious immature virus particle composed of Gag polyproteins. Transition to the mature infectious particle is triggered by a protease, which cuts Gag to individual domains. Decades of research described this process in atomic detail. 2/x
November 12, 2024 at 9:04 PM
HIV-1 buds from the host cell as a non-infectious immature virus particle composed of Gag polyproteins. Transition to the mature infectious particle is triggered by a protease, which cuts Gag to individual domains. Decades of research described this process in atomic detail. 2/x
Our new preprint from Briggs lab is out! We solved the in-virus #cryoEM structure of the HIV matrix protein by SPA. The structure led us to a discovery resolving a long mystery in HIV biology – a peptide SP2 triggers the maturation of the HIV matrix domain. A 🧵 1/x
Paper: tinyurl.com/c7szhtfa
Paper: tinyurl.com/c7szhtfa
November 12, 2024 at 9:04 PM
Our new preprint from Briggs lab is out! We solved the in-virus #cryoEM structure of the HIV matrix protein by SPA. The structure led us to a discovery resolving a long mystery in HIV biology – a peptide SP2 triggers the maturation of the HIV matrix domain. A 🧵 1/x
Paper: tinyurl.com/c7szhtfa
Paper: tinyurl.com/c7szhtfa
