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Reposted by Samuel Maiwald

Nature Chemical Biology @natchembio.nature.com · Aug 18

A new paper reports the structure of the E4 enzyme Ufd2, which mediates K48 branched ubiquitination on K29diUb and K29triUb, identifying Ufd2’s core region as a K29diUb binding domain and a dimeric conformation for distal ubiquitin stabilization

www.nature.com/articles/s41...

Structural basis for E4 enzyme Ufd2-catalyzed K48/K29 branched ubiquitin chains - Nature Chemical Biology

Tong et al. chemically trapped the structure of the E4 enzyme Ufd2, which mediates K48 branched ubiquitination on K29diUb and K29triUb, identifying Ufd2’s core region as a K29diUb binding domain and a...

www.nature.com

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Reposted by Samuel Maiwald

Carolin Klose @carolinklose.bsky.social · Aug 11

Super excited to share our new #preprint on #BioRxiv ✨
We reveal the structural basis of a partnership between the ER membrane complex (EMC) and the P5A-ATPase Spf1 — an insertase–dislocase duo that coordinates membrane protein biogenesis and quality control.
www.biorxiv.org/content/10.1...

Structural basis of an EMC:Spf1 insertase-dislocase complex in the eukaryotic endoplasmic reticulum

Most eukaryotic membrane proteins are inserted into the membrane at the endoplasmic reticulum (ER). This essential but error-prone process relies on molecular quality control machineries to prevent mi...

www.biorxiv.org

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Reposted by Samuel Maiwald

Carolin Klose @carolinklose.bsky.social · Aug 5

Excited to share our latest study in @natcomms.nature.com , where we characterize the chaperone function of the ER membrane protein complex (EMC)—supporting membrane protein biogenesis beyond insertion!
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www.nature.com/articles/s41...

The EMC acts as a chaperone for membrane proteins - Nature Communications

Membrane proteins are essential for any cell but difficult to fold. Here, the authors show that the EMC acts as a chaperone for membrane proteins. They dissect client recognition and provide a molecul...

www.nature.com

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Reposted by Samuel Maiwald

Leo Kiss @leokiss.bsky.social · Jun 2

Schulman lab is ready for the GRK2243 Symposium: Understanding ubiquitination: from molecular mechanisms to disease in würzburg

#wUeBI2025 @grk2243.bsky.social
@jakobfarnung.bsky.social @samuelmaiwald.bsky.social @hannahbkmpr.bsky.social

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Thank you!

Reposted by Samuel Maiwald

Max Planck Institute of Biochemistry @mpibiochem.bsky.social · May 26

Check out our latest study @natsmb.nature.com‬: Establishing a consensus model for #ubiquitin chain assembly by HECT #E3 ligases: #cryoEM structures of #TRIP12 forming K29-linked and K29/K48-branched chains!

❕ www.nature.com/articles/s41...

@samuelmaiwald.bsky.social @unileiden.bsky.social

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Reposted by Samuel Maiwald

Nature Structural & Molecular Biology @natsmb.nature.com · May 26

New online: TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains

Nature Structural & Molecular Biology, Published online: 26 May 2025; doi:10.1038/s41594-025-01561-1Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation shared by some HECT E3s.

go.nature.com

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Thank you Dawa! :)

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Thank you Jakob! :)

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Thanks Leo! :)

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Many thanks to Brenda and all other coauthors from the Schulman lab @mpibiochem.bsky.social as well as our collaborators Matthew and Monique ‪@unileiden.bsky.social‬, who made this work possible!

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Comparison to our previous structure showing K48 chain formation by UBR5 suggests a consensus architecture for linkage-specific chain formation by HECT E3s.

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

On the other side, acceptor and donor ubiquitins come together with the TRIP12 HECT domain to establish the active site. Both sides cooperate to precisely place K29 of the proximal acceptor ubiquitin for catalysis.

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

One TRIP12 side avidly recruits the K48-linked chain, explaining preference for the proximal ubiquitin.

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

We used activity-based probes to trap TRIP12 in the act of forming a K29/K48-branched triUb and a K29-linked diUb. Visualizing these complexes using cryo-EM revealed TRIP12s catalytic mechanism.

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

TRIP12 adds K29-linked ubiquitin onto K48-linked ubiquitin chains. We show that TRIP12 preferentially modifies the proximal ubiquitin to form branched chains.

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Excited to share our latest study on how K29/K48-branched #ubiquitin chains are forged by the #E3 ligase TRIP12, and how this suggests a consensus mechanism for chain formation by HECT E3s!

@natsmb.nature.com

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www.nature.com/articles/s41...

TRIP12 structures reveal HECT E3 formation of K29 linkages and branched ubiquitin chains - Nature Structural & Molecular Biology

Using biochemistry, chemical biology, and cryo-EM, Maiwald et al. elucidate how TRIP12 forms K29 linkages and K29/K48-linked branched ubiquitin chains, revealing a mechanism for polyubiquitylation sha...

www.nature.com

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Samuel Maiwald @samuelmaiwald.bsky.social · May 26

@natsmb.nature.com

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Many thanks to Brenda and all other coauthors from the Schulman lab @mpibiochem.bsky.social as well as our collaborators Matthew and Monique ‪@unileiden.bsky.social‬, who made this work possible!

7/7

1

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

Comparison to our previous structure showing K48 chain formation by UBR5 suggests a consensus architecture for linkage-specific chain formation by HECT E3s.

6/7

1

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

On the other side, acceptor and donor ubiquitins come together with the TRIP12 HECT domain to establish the active site. Both sides cooperate to precisely place K29 of the proximal acceptor ubiquitin for catalysis.

5/7

1 1

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

One TRIP12 side avidly recruits the K48-linked chain, explaining preference for the proximal ubiquitin.

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1 1

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

We used activity-based probes to trap TRIP12 in the act of forming a K29/K48-branched triUb and a K29-linked diUb. Visualizing these complexes using cryo-EM revealed TRIP12s catalytic mechanism.

3/7

1 1

Samuel Maiwald @samuelmaiwald.bsky.social · May 26

TRIP12 adds K29-linked ubiquitin onto K48-linked ubiquitin chains. We show that TRIP12 preferentially modifies the proximal ubiquitin to form branched chains.

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Reposted by Samuel Maiwald

Leo Kiss @leokiss.bsky.social · Mar 24

Super excited to share our latest work on deciphering the #Ubiquitin Code

“𝗨𝗯𝗶𝗥𝗘𝗔𝗗 𝗱𝗲𝗰𝗶𝗽𝗵𝗲𝗿𝘀 𝗽𝗿𝗼𝘁𝗲𝗮𝘀𝗼𝗺𝗮𝗹 𝗱𝗲𝗴𝗿𝗮𝗱𝗮𝘁𝗶𝗼𝗻 𝗰𝗼𝗱𝗲 𝗼𝗳 𝗵𝗼𝗺𝗼𝘁𝘆𝗽𝗶𝗰 𝗮𝗻𝗱 𝗯𝗿𝗮𝗻𝗰𝗵𝗲𝗱 𝗞48 𝗮𝗻𝗱 𝗞63 𝘂𝗯𝗶𝗾𝘂𝗶𝘁𝗶𝗻 𝗰𝗵𝗮𝗶𝗻𝘀”

@cp-molcell.bsky.social

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www.cell.com/molecular-ce...

UbiREAD deciphers proteasomal degradation code of homotypic and branched K48 and K63 ubiquitin chains

Ubiquitin chains determine the fates of their modified proteins, including proteasomal degradation. Kiss et al. present UbiREAD, a technology to monitor cellular degradation and deubiquitination at hi...

www.cell.com

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