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Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping

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  • Yida Jiang

    (Peking University)

  • Xinghe Zhang

    (Peking University)

  • Honggang Nie

    (Peking University
    Peking University)

  • Jianxiong Fan

    (Peking University)

  • Shuangshuang Di

    (Peking University
    Peking University)

  • Hui Fu

    (Peking University
    Peking University)

  • Xiu Zhang

    (Peking University
    Peking University)

  • Lijuan Wang

    (Peking University
    Peking University)

  • Chun Tang

    (Peking University
    Peking University)

Abstract

While photo-cross-linking (PXL) with alkyl diazirines can provide stringent distance restraints and offer insights into protein structures, unambiguous identification of cross-linked residues hinders data interpretation to the same level that has been achieved with chemical cross-linking (CXL). We address this challenge by developing an in-line system with systematic modulation of light intensity and irradiation time, which allows for a quantitative evaluation of diazirine photolysis and photo-reaction mechanism. Our results reveal a two-step pathway with mainly sequential generation of diazo and carbene intermediates. Diazo intermediate preferentially targets buried polar residues, many of which are inaccessible with known CXL probes for their limited reactivity. Moreover, we demonstrate that tuning light intensity and duration enhances selectivity towards polar residues by biasing diazo-mediated cross-linking reactions over carbene ones. This mechanistic dissection unlocks the full potential of PXL, paving the way for accurate distance mapping against protein structures and ultimately, unveiling protein dynamic behaviors.

Suggested Citation

  • Yida Jiang & Xinghe Zhang & Honggang Nie & Jianxiong Fan & Shuangshuang Di & Hui Fu & Xiu Zhang & Lijuan Wang & Chun Tang, 2024. "Dissecting diazirine photo-reaction mechanism for protein residue-specific cross-linking and distance mapping," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50315-y
    DOI: 10.1038/s41467-024-50315-y
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    References listed on IDEAS

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    1. Lucio Manzi & Andrew S. Barrow & Daniel Scott & Robert Layfield & Timothy G. Wright & John E. Moses & Neil J. Oldham, 2016. "Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions," Nature Communications, Nature, vol. 7(1), pages 1-9, December.
    2. Zhen-Lin Chen & Jia-Ming Meng & Yong Cao & Ji-Li Yin & Run-Qian Fang & Sheng-Bo Fan & Chao Liu & Wen-Feng Zeng & Yue-He Ding & Dan Tan & Long Wu & Wen-Jing Zhou & Hao Chi & Rui-Xiang Sun & Meng-Qiu Do, 2019. "A high-speed search engine pLink 2 with systematic evaluation for proteome-scale identification of cross-linked peptides," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    3. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
    4. Jian-Hua Wang & Yu-Liang Tang & Zhou Gong & Rohit Jain & Fan Xiao & Yu Zhou & Dan Tan & Qiang Li & Niu Huang & Shu-Qun Liu & Keqiong Ye & Chun Tang & Meng-Qiu Dong & Xiaoguang Lei, 2022. "Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Swantje Lenz & Ludwig R. Sinn & Francis J. O’Reilly & Lutz Fischer & Fritz Wegner & Juri Rappsilber, 2021. "Reliable identification of protein-protein interactions by crosslinking mass spectrometry," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    6. Zhenming Jin & Xiaoyu Du & Yechun Xu & Yongqiang Deng & Meiqin Liu & Yao Zhao & Bing Zhang & Xiaofeng Li & Leike Zhang & Chao Peng & Yinkai Duan & Jing Yu & Lin Wang & Kailin Yang & Fengjiang Liu & Re, 2020. "Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors," Nature, Nature, vol. 582(7811), pages 289-293, June.
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