@LabZheng

Ning Zheng Laboratory at University of Washington

Joined August 2019
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Two decades after revealing the mechanism of action of auxin, we have now uncovered the molecular mystery of another plant hormone: salicylic acid (SA), the precursor of aspirin that most of us have taken at some point in our lives. We were surprised again rdcu.be/EbdVwEStSHha
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Excited to share our lab's latest discovery today in @Nature: "orthosteric molecular glue” (OMG) inhibitors - a new drug design strategy that achieves substrate-dependent potency, i.e., substrate selectivity, with conventional orthosteric inhibitors. rdcu.be/e3waV
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We are still in awe that the "" effect allows this to happen!
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By selectively inhibiting an enzyme’s activity toward a specific disease-relevant substrate while sparing others, OMG inhibitors could provide a more refined alternative in drug design - enabling the development of treatments that are more effective & better tolerated by patients
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Together with Michele Pagano's lab at NYU, we are excited to share a new story on two F-box protein E3 ligases recognizing two distinct & mutually exclusive degrons encrypted in the quaternary structure of the substrate protein biorxiv.org/content/10.1101/…

Distinct Perception Mechanisms of BACH1 Quaternary Structure Degrons by Two F-box Proteins under...

The transcription factor BACH1 regulates heme homeostasis and oxidative stress responses and promotes cancer metastasis upon aberrant accumulation. Its stability is controlled by two F-box protein...

biorxiv.org
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Story 1: UM171 asymmetrically reprograms dimeric CRL3-KBTBD4 to degrade CoREST via HDAC1/2 with InsP6 as a second glue. Story (2): Cancer mutations of KBTBD4 found in medulloblastoma structurally, functionally, and mechanistically mimic UM171. biorxiv.org/content/10.1101/…

KBTBD4 Cancer Hotspot Mutations Drive Neomorphic Degradation of HDAC1/2 Corepressor Complexes

Cancer mutations can create neomorphic protein-protein interactions to drive aberrant function[1][1]. As a substrate receptor of the CULLIN3-RBX1 E3 ubiquitin ligase complex, KBTBD4 is recurrently...

biorxiv.org
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Together with labs of @brian_b_liau and Philip Cole and many other collaborators, we are excited to share a new molecular glue story with many surprises. biorxiv.org/content/10.1101/…

Asymmetric Engagement of Dimeric CRL3KBTBD4 by the Molecular Glue UM171 Licenses Degradation of...

UM171 is a potent small molecule agonist of ex vivo human hematopoietic stem cell (HSC) self-renewal[1][1], a process that is tightly controlled by epigenetic regulation. By co-opting KBTBD4, a...

biorxiv.org
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We now formally define #molecularglue after coining the term for the MoA of #auxin in 2007. nature.com/articles/s41467-0…
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Welcome, two new postdocs Songwen and Mark joined our lab!
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Open-state structure and pore gating mechanism of the cardiac sodium channel cell.com/cell/fulltext/S0092…
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Finally! Many thanks to my Ph.D. supervisor Dr. Xinzheng Zhang and my labmate Ph.D. candidate Chunling Wu. Low-cooling-rate freezing in biomolecular cryo-electron microscopy for recovery of initial frames cup.org/3hg2bxN
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We are hiring!!! Please RT: A postdoc position is now open in our growing lab @ShabekLab (@ucdavis California) to study the structure-function of hormone signaling pathway and the ubiquitin system. #structuralbiology #postdocjobs #ubiquitin #Biochemistry #plantbiology
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As part of our first entry into the Twitter world, we are happy to present our first preprint!
bioRxiv@biorxivpreprint
20 Aug 2019
Structural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS biorxiv.org/cgi/content/shor… #bioRxiv
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