Volume 8 Issue 5-6
Dec.  2022
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Jian-Hua Wang, Zhou Gong, Xu Dong, Shu-Qun Liu, Yu-Liang Tang, Xiaoguang Lei, Chun Tang, Meng-Qiu Dong. Fast cross-linking by DOPA2 promotes the capturing of a stereospecific protein complex over nonspecific encounter complexes[J]. Biophysics Reports, 2022, 8(5-6): 239-252. doi: 10.52601/bpr.2022.220014
Citation: Jian-Hua Wang, Zhou Gong, Xu Dong, Shu-Qun Liu, Yu-Liang Tang, Xiaoguang Lei, Chun Tang, Meng-Qiu Dong. Fast cross-linking by DOPA2 promotes the capturing of a stereospecific protein complex over nonspecific encounter complexes[J]. Biophysics Reports, 2022, 8(5-6): 239-252. doi: 10.52601/bpr.2022.220014

Fast cross-linking by DOPA2 promotes the capturing of a stereospecific protein complex over nonspecific encounter complexes

doi: 10.52601/bpr.2022.220014
Funds:  We thank Yulu Li and Dr. Jianhua Sui for the help in determining the KD value of EIIAGlc/EIIBGlc. We gratefully acknowledge financial support from the following grants: Development of Major Scientific Instruments and Equipment of China (2020YFF01014505 to M.-Q.D.), the National Key Research and Development Program (2018YFA0507700 to C.T.), the National Natural Science Foundation of China (22161132013 to C.T.) and the Program for Donglu Scholar in the Yunnan University (to S.-Q. L).
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  • Author Bio:

    Jian-Hua Wang and

    Zhou Gong contributed equally to this work

  • Corresponding author: Tang_Chun@pku.edu.cndongmengqiu@nibs.ac.cn
  • Received Date: 22 June 2022
  • Accepted Date: 17 October 2022
  • Available Online: 17 February 2023
  • Publish Date: 31 December 2022
  • Transient and weak protein–protein interactions are essential to many biochemical reactions, yet are technically challenging to study. Chemical cross-linking of proteins coupled with mass spectrometry analysis (CXMS) provides a powerful tool in the analysis of such interactions. Central to this technology are chemical cross-linkers. Here, using two transient heterodimeric complexes EIN/HPr and EIIAGlc/EIIBGlc as our model systems, we evaluated the effects of two amine-specific homo-bifunctional cross-linkers with different reactivities. We showed previously that DOPA2 (di-ortho-phthalaldehyde with a di-ethylene glycol spacer arm) cross-links proteins 60–120 times faster than DSS (disuccinimidyl suberate). We found that though most of the intermolecular cross-links of either cross-linker are consistent with the encounter complexes (ECs), an ensemble of short-lived binding intermediates, more DOPA2 intermolecular cross-links could be assigned to the stereospecific complex (SC), the final lowest-energy conformational state for the two interacting proteins. Our finding suggests that faster cross-linking captures the SC more effectively and cross-linkers of different reactivities potentially probe protein–protein interaction dynamics across multiple timescales.

  • Jian-Hua Wang, Zhou Gong, Xu Dong, Shu-Qun Liu, Yu-Liang Tang, Xiaoguang Lei, Chun Tang and Meng-Qiu Dong declare that they have no conflict of interest.
    This article does not contain any studies with human or animal subjects performed by any of the authors.

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