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 LATEST RESEARCH 2024 

• Transport and inhibition mechanisms of human VMAT2
  • Di Wu
  • Qihao Chen
  • Daohua Jiang

 

• De novo design of high-affinity binders of bioactive helical peptides
  • Susana Vázquez Torres
  • Philip J. Y. Leung
  • David Baker

 

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Multiple redox switches of the SARS-CoV-2 main protease in vitro provide opportunities for drug design

Here the authors demonstrate that the SARS-CoV-2 main protease (Mpro) is subject to redox regulation in vitro, reversibly switching between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues.

• • Lisa-Marie Funk
  • Gereon Poschmann
  • Kai Tittmann

 

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Natural product P57 induces hypothermia through targeting pyridoxal kinase

Induction of hypothermia during hibernation/torpor enables certain mammals to survive under extreme conditions. Here, the authors show that the natural product P57 induces hypothermia by targeting pyridoxal kinase and has a potential application in therapeutic hypothermia.

• • Ruina Wang
  • Lei Xiao
  • Yongjun Dang

 

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Enantioselective decarboxylative alkylation using synergistic photoenzymatic catalysis

Merging photoredox and biocatalysis provides opportunities to address challenges in synthetic chemistry. Now the combination of a ruthenium photocatalyst for oxidative radical formation and ‘ene’-reductases for radical interception enables an enantiodivergent decarboxylative alkylation reaction.

• • Shang-Zheng Sun
  • Bryce T. Nicholls
  • Todd K. Hyster

 

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Structure and dynamics of endogenous cardiac troponin complex in human heart tissue captured by native nanoproteomics

The heterogenous nature and dynamics of endogenous protein complexes pose challenges for conventional structural biology techniques. Here, the authors develop a native nanoproteomics strategy for the enrichment and subsequent native top-down mass spectrometry (nTDMS) analysis of endogenous cardiac troponin (cTn) complex directly from human heart tissue.

• • Emily A. Chapman
  • David S. Roberts
  • Ying Ge

 

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Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE

Transmembrane E3 ligases are crucial in cellular homeostasis and metabolic regulation. Here, the authors provide the structural details of the ER-resident E3 ligase MARCH6/Doa10, uncovering its unique circular membrane structure and its role in ubiquitylation processes, essential for protein quality control.

• • J. Josephine Botsch
  • Roswitha Junker
  • Bastian Bräuning

 

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Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system

Short prokaryotic Argonaute and Sir2 proteins function as an antivirus system. Here the authors describe structures of SPARSA (a heterodimer of Sir2-APAZ and prokaryotic Argonaute) with and without template DNA and guide RNA, providing structural basis of its assembly and activation by the recognition of the invading virus.

• • Xiangkai Zhen
  • Xiaolong Xu
  • Songying Ouyang

 

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Massively parallel profiling of RNA-targeting CRISPR-Cas13d

Systematic understanding of CRISPR enzyme RNA binding specificity and cleavage is lacking. Here the authors report RNA chip-hybridised association-mapping platform (RNA-CHAMP), a workflow that repurposes next generation DNA sequencing chips to measure the binding affinity for RNA targets.

• • Hung-Che Kuo
  • Joshua Prupes
  • Ilya J. Finkelstein

 

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Native metabolomics identifies the rivulariapeptolide family of protease inhibitors

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

• • Raphael Reher
  • Allegra T. Aron
  • Daniel Petras

 

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Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners

Here, the authors investigate the maturation of human respiratory Complex II, uncovering two metastable intermediates of maturation which suggest changes in intrinsic disorder ensure that the assembly steps occur in the correct sequence.

• • Pankaj Sharma
  • Elena Maklashina
  • T. M. Iverson

 

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Native mass spectrometry reveals the initial binding events of HIV-1 rev to RRE stem II RNA

The HIV-1 RNA-binding protein rev facilitates nuclear export of viral RNA. Here, the authors use native mass spectrometry to study the interactions between rev-derived peptides and rev response elements of HIV-1 RNA, providing mechanistic insights into rev recognition and recruitment.

• • Eva-Maria Schneeberger
  • Matthias Halper
  • Kathrin Breuker
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