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

Jian-Hua Wang; Zhou Gong; Xu Dong; Shu-Qun Liu; Yu-Liang Tang; Xiaoguang Lei; Chun Tang; Meng-Qiu Dong

doi:10.52601/bpr.2022.220014

Volume 8 Issue 5-6

Dec. 2022

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Article Navigation > Biophysics Reports > 2022 > 8(5-6): 239-252

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

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

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

doi: 10.52601/bpr.2022.220014

Jian-Hua Wang^{1, 2},
Zhou Gong³,
Xu Dong³,
Shu-Qun Liu⁴,
Yu-Liang Tang⁵,
Xiaoguang Lei⁵,
Chun Tang^{5
,
,},
Meng-Qiu Dong^{1, 2
,
,}

1.
National Institute of Biological Sciences (NIBS), Beijing 102206, China
2.
Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China
3.
State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China
4.
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650091, China
5.
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Center for Quantitative Biology, Peking-Tsinghua Center for Life Science, Peking University, Beijing 100871, China

Funds: We thank Yulu Li and Dr. Jianhua Sui for the help in determining the K_D value of EIIA^Glc/EIIB^Glc. 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.cn; dongmengqiu@nibs.ac.cn
Received Date: 22 June 2022
Accepted Date: 17 October 2022

Available Online: 17 February 2023

Publish Date: 31 December 2022

Abstract

Abstract

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 EIIA^Glc/EIIB^Glc 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.
- Chemical cross-linking,
- Mass spectrometry,
- Transient protein–protein interaction,
- Encounter complexes,
- Stereospecific complex,
- Cross-linker,
- DOPA2,
- DSS

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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References(50)

References

Acuner Ozbabacan SE, Engin HB, Gursoy A, Keskin O (2011) Transient protein-protein interactions. Protein Eng Des Sel 24(9): 635−648 doi: 10.1093/protein/gzr025

Anthis NJ, Clore GM (2015) Visualizing transient dark states by NMR spectroscopy. Q Rev Biophys 48(1): 35−116 doi: 10.1017/S0033583514000122

Belsom A, Rappsilber J (2021) Anatomy of a crosslinker. Curr Opin Chem Biol 60: 39−46 doi: 10.1016/j.cbpa.2020.07.008

Berggard T, Linse S, James P (2007) Methods for the detection and analysis of protein-protein interactions. Proteomics 7(16): 2833−2842 doi: 10.1002/pmic.200700131

Cai M, Williams DC, Jr., Wang G, Lee BR, Peterkofsky A, Clore GM (2003) Solution structure of the phosphoryl transfer complex between the signal-transducing protein IIAGlucose and the cytoplasmic domain of the glucose transporter IICBGlucose of the Escherichia coli glucose phosphotransferase system. J Biol Chem 278(27): 25191−25206 doi: 10.1074/jbc.M302677200

Chavez JD, Bruce JE (2019) Chemical cross-linking with mass spectrometry: a tool for systems structural biology. Curr Opin Chem Biol 48: 8−18 doi: 10.1016/j.cbpa.2018.08.006

Chen ZL, Meng JM, Cao Y, Yin JL, Fang RQ, Fan SB, Liu C, Zeng WF, Ding YH, Tan D, Wu L, Zhou WJ, Chi H, Sun RX, Dong MQ, He SM (2019) A high-speed search engine pLink 2 with systematic evaluation for proteome-scale identification of cross-linked peptides. Nat Commun 10(1): 3404. https://doi.org/10.1038/s41467-019-11337-z

Combe CW, Fischer L, Rappsilber J (2015) xiNET: cross-link network maps with residue resolution. Mol Cell Proteomics 14(4): 1137−1147 doi: 10.1074/mcp.O114.042259

Deutscher J, Francke C, Postma PW (2006) How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol Mol Biol Rev 70(4): 939−1031 doi: 10.1128/MMBR.00024-06

Ding YH, Fan SB, Li S, Feng BY, Gao N, Ye K, He SM, Dong MQ (2016) Increasing the depth of mass-spectrometry-based structural analysis of protein complexes through the use of multiple cross-Linkers. Anal Chem 88(8): 4461−4469 doi: 10.1021/acs.analchem.6b00281

Dong X, Qin LY, Gong Z, Qin S, Zhou HX, Tang C (2022) Preferential interactions of a crowder protein with the specific binding site of a native protein complex. J Phys Chem Lett 13(3): 792−800 doi: 10.1021/acs.jpclett.1c03794

Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, Ji XL, Liu SQ (2016) Insights into protein-ligand interactions: mechanisms, models, and methods. Int J Mol Sci 17(2): 144. https://doi.org/10.3390/ijms17020144

Fan SB, Wu YJ, Yang B, Chi H, Meng JM, Lu S, Zhang K, Wu L, Sun RX, Dong MQ, He SM (2014) A new approach to protein structure and interaction research: chemical cross-linking in combination with mass spectrometry. Prog Biochem Biophys 41(11): 1109−1125

Fawzi NL, Doucleff M, Suh JY, Clore GM (2010) Mechanistic details of a protein-protein association pathway revealed by paramagnetic relaxation enhancement titration measurements. Proc Natl Acad Sci USA 107(4): 1379−1384 doi: 10.1073/pnas.0909370107

Garrett DS, Seok YJ, Peterkofsky A, Clore GM, Gronenborn AM (1997) Identification by NMR of the binding surface for the histidine-containing phosphocarrier protein HPr on the N-terminal domain of enzyme I of the Escherichia coli phosphotransferase system. Biochemistry 36(15): 4393−4398 doi: 10.1021/bi970221q

Garrett DS, Seok YJ, Peterkofsky A, Gronenborn AM, Clore GM (1999) Solution structure of the 40,000 Mr phosphoryl transfer complex between the N-terminal domain of enzyme I and HPr. Nat Struct Biol 6(2): 166−173 doi: 10.1038/5854

Gong Z, Ding YH, Dong X, Liu N, Zhang EE, Dong MQ, Tang C (2015) Visualizing the ensemble structures of protein complexes using chemical cross-linking coupled with mass spectrometry. Biophys Rep 1: 127−138 doi: 10.1007/s41048-015-0015-y

Gong Z, Ye SX, Nie ZF, Tang C (2020) The conformational preference of chemical cross-linkers determines the cross-linking probability of reactive protein residues. J Phys Chem B 124(22): 4446−4453 doi: 10.1021/acs.jpcb.0c02522

Herzog F, Kahraman A, Boehringer D, Mak R, Bracher A, Walzthoeni T, Leitner A, Beck M, Hartl FU, Ban N, Malmstrom L, Aebersold R (2012) Structural probing of a protein phosphatase 2A network by chemical cross-linking and mass spectrometry. Science 337(6100): 1348−1352 doi: 10.1126/science.1221483

Hofmann T, Fischer AW, Meiler J, Kalkhof S (2015) Protein structure prediction guided by crosslinking restraints-a systematic evaluation of the impact of the crosslinking spacer length. Methods 89: 79−90 doi: 10.1016/j.ymeth.2015.05.014

Kastner B, Fischer N, Golas MM, Sander B, Dube P, Boehringer D, Hartmuth K, Deckert J, Hauer F, Wolf E, Uchtenhagen H, Urlaub H, Herzog F, Peters JM, Poerschke D, Luhrmann R, Stark H (2008) GraFix: sample preparation for single-particle electron cryomicroscopy. Nat Methods 5(1): 53−55 doi: 10.1038/nmeth1139

Kotrba P, Inui M, Yukawa H (2001) Bacterial phosphotransferase system (PTS) in carbohydrate uptake and control of carbon metabolism. J Biosci Bioeng 92(6): 502−517 doi: 10.1016/S1389-1723(01)80308-X

Kozakov D, Li K, Hall DR, Beglov D, Zheng J, Vakili P, Schueler-Furman O, Paschalidis I, Clore GM, Vajda S (2014) Encounter complexes and dimensionality reduction in protein-protein association. Elife 3: e01370. https://doi.org/10.7554/eLife.01370

La D, Kong M, Hoffman W, Choi YI, Kihara D (2013) Predicting permanent and transient protein-protein interfaces. Proteins 81(5): 805−818 doi: 10.1002/prot.24235

Liu F, Heck AJ (2015) Interrogating the architecture of protein assemblies and protein interaction networks by cross-linking mass spectrometry. Curr Opin Struct Biol 35: 100−108 doi: 10.1016/j.sbi.2015.10.006

Liu Z, Gong Z, Dong X, Tang C (2016) Transient protein-protein interactions visualized by solution NMR. Biochim Biophys Acta 1864(1): 115−122 doi: 10.1016/j.bbapap.2015.04.009

Lv L, Chen P, Cao L, Li Y, Zeng Z, Cui Y, Wu Q, Li J, Wang JH, Dong MQ, Qi X, Han T (2020) Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation. Elife 9: e59994. https://doi.org/10.7554/eLife.59994

Matthew Allen Bullock J, Schwab J, Thalassinos K, Topf M (2016) The importance of non-accessible crosslinks and solvent accessible surface distance in modeling proteins with restraints from crosslinking mass spectrometry. Mol Cell Proteomics 15(7): 2491−2500 doi: 10.1074/mcp.M116.058560

O'Reilly FJ, Rappsilber J (2018) Cross-linking mass spectrometry: methods and applications in structural, molecular and systems biology. Nat Struct Mol Biol 25(11): 1000−1008 doi: 10.1038/s41594-018-0147-0

Perkins JR, Diboun I, Dessailly BH, Lees JG, Orengo C (2010) Transient protein-protein interactions: structural, functional, and network properties. Structure 18(10): 1233−1243 doi: 10.1016/j.str.2010.08.007

Qin J, Gronenborn AM (2014) Weak protein complexes: challenging to study but essential for life. FEBS J 281(8): 1948−1949 doi: 10.1111/febs.12744

Reizer J, Sutrina SL, Wu LF, Deutscher J, Reddy P, Saier MH, Jr. (1992) Functional interactions between proteins of the phosphoenolpyruvate: sugar phosphotransferase systems of Bacillus subtilis and Escherichia coli. J Biol Chem 267(13): 9158−9169 doi: 10.1016/S0021-9258(19)50403-3

Schilder J, Ubbink M (2013) Formation of transient protein complexes. Curr Opin Struct Biol 23(6): 911−918 doi: 10.1016/j.sbi.2013.07.009

Shi Y, Pellarin R, Fridy PC, Fernandez-Martinez J, Thompson MK, Li Y, Wang QJ, Sali A, Rout MP, Chait BT (2015) A strategy for dissecting the architectures of native macromolecular assemblies. Nat Methods 12(12): 1135−1138 doi: 10.1038/nmeth.3617

Smith GP (1985) Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science 228(4705): 1315−1317 doi: 10.1126/science.4001944

Suh JY, Tang C, Clore GM (2007) Role of electrostatic interactions in transient encounter complexes in protein-protein association investigated by paramagnetic relaxation enhancement. J Am Chem Soc 129(43): 12954−12955 doi: 10.1021/ja0760978

Tang C, Gong Z (2020) Integrating non-NMR distance restraints to augment NMR depiction of protein structure and dynamics. J Mol Biol 432(9): 2913−2929 doi: 10.1016/j.jmb.2020.01.023

Tang C, Iwahara J, Clore GM (2006) Visualization of transient encounter complexes in protein-protein association. Nature 444(7117): 383−386 doi: 10.1038/nature05201

Vaynberg J, Qin J (2006) Weak protein-protein interactions as probed by NMR spectroscopy. Trends Biotechnol 24(1): 22−27 doi: 10.1016/j.tibtech.2005.09.006

Wang JH, Tang YL, Gong Z, Jain R, Xiao F, Zhou Y, Tan D, Li Q, Huang N, Liu SQ, Ye K, Tang C, Dong MQ, Lei X (2022) Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers. Nat Commun 13(1): 1468. https://doi.org/10.1038/s41467-022-28879-4

Wheat A, Yu C, Wang X, Burke AM, Chemmama IE, Kaake RM, Baker P, Rychnovsky SD, Yang J, Huang L (2021) Protein interaction landscapes revealed by advanced in vivo cross-linking-mass spectrometry. Proc Natl Acad Sci USA 118(32): e2023360118. https://doi.org/10.1073/pnas.2023360118

Wu S, Tan D, Woolford JL, Jr., Dong MQ, Gao N (2017) Atomic modeling of the ITS2 ribosome assembly subcomplex from cryo-EM together with mass spectrometry-identified protein-protein crosslinks. Protein Sci 26(1): 103−112 doi: 10.1002/pro.3045

Xing Q, Huang P, Yang J, Sun JQ, Gong Z, Dong X, Guo DC, Chen SM, Yang YH, Wang Y, Yang MH, Yi M, Ding YM, Liu ML, Zhang WP, Tang C (2014) Visualizing an ultra-weak protein-protein interaction in phosphorylation signaling. Angew Chem Int Ed Engl 53(43): 11501−11505 doi: 10.1002/anie.201405976

Yang B, Wu H, Schnier PD, Liu Y, Liu J, Wang N, DeGrado WF, Wang L (2018) Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry. Proc Natl Acad Sci USA 115(44): 11162−11167 doi: 10.1073/pnas.1813574115

Yang B, Wu YJ, Zhu M, Fan SB, Lin J, Zhang K, Li S, Chi H, Li YX, Chen HF, Luo SK, Ding YH, Wang LH, Hao Z, Xiu LY, Chen S, Ye K, He SM, Dong MQ (2012) Identification of cross-linked peptides from complex samples. Nat Methods 9(9): 904−906 doi: 10.1038/nmeth.2099

Yu C, Huang L (2018) Cross-linking mass spectrometry: an emerging technology for interactomics and structural biology. Anal Chem 90(1): 144−165 doi: 10.1021/acs.analchem.7b04431

Yu C, Novitsky EJ, Cheng NW, Rychnovsky SD, Huang L (2020) Exploring spacer arm structures for designs of asymmetric sulfoxide-containing MS-cleavable cross-Linkers. Anal Chem 92(8): 6026−6033 doi: 10.1021/acs.analchem.0c00298

Zhao K, Cheng S, Miao N, Xu P, Lu X, Zhang Y, Wang M, Ouyang X, Yuan X, Liu W, Lu X, Zhou P, Gu J, Zhang Y, Qiu D, Jin Z, Su C, Peng C, Wang JH, Dong MQ, Wan Y, Ma J, Cheng H, Huang Y, Yu Y (2019) A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation. Nat Cell Biol 21(10): 1261−1272 doi: 10.1038/s41556-019-0396-0

Zhao Q, Zhou H, Chi S, Wang Y, Wang J, Geng J, Wu K, Liu W, Zhang T, Dong MQ, Wang J, Li X, Xiao B (2018) Structure and mechanogating mechanism of the Piezo1 channel. Nature 554(7693): 487−492 doi: 10.1038/nature25743

Ziemianowicz DS, Ng D, Schryvers AB, Schriemer DC (2019) Photo-cross-linking mass spectrometry and integrative modeling enables rapid screening of antigen interactions involving bacterial transferrin receptors. J Proteome Res 18(3): 934−946 doi: 10.1021/acs.jproteome.8b00629

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