Paul Xiang-Qin Liu

Education

• PhD, Cornell University

Academic Positions

• Department member since 1989
• Honours Research Project Coordinator (2022 - present)

Research Topics:

Intein-catalyzed protein splicing and applications in recombinant protein engineering, site-specific modification, peptide cyclization, and artificial spider silks

Research

Protein Splicing and Inteins.

Our main interests are to develop intein-based protein splicing technologies for various protein applications and to understand intein's structure-function. Inteins are protein intervening sequences that can self-excise through protein splicing. Over 500 inteins have been found in various host proteins of various organisms, and there are also intein-related protein processing in human. Crystal structures of inteins revealed a conserved splicing domain of ~130 aa in size, although most inteins also have an endonuclease domain involved in the evolutionary mobility of inteins. A current focus is on split inteins that can piece together separate polypeptides through protein trans-splicing, which are useful in various forms of protein and peptide ligation. Examples of intein-based technologies include protein function control through conditional splicing, protein synthesis and modification through protein and/or peptide ligation, protein and peptide cyclization, and protein productions in certain gene therapy and in transgenic plant procedures. The possibilities of intein-based applications are limited only by one's imagination, and they can be better explored through a deeper understanding of intein structure-function.

Publications

1. Baker, L.A., Xu, L., Badichi Akher, F., Robertson, M.K., Pugsley-DeBruyn, L., Ma, C.X., Liu, X-Q., Frampton, J.P., and Rainey, J.K. (2022) Nerve growth factor-binding engineered silk films promote neuronal attachment and neurite outgrowth. Advanced Functional Materials. In press. [Article]
2. Song, Q., Liu, X-Q., and Rainey, J.K. (2022) The MDMX acidic domain competes with the p53 transactivation domain for MDM2 N-terminal domain binding. Biochim Biophys Acta Mol Cell Res. 1869: 119319. [PubMed] [Article]
3. Song, Q., Liu, X-Q., and Rainey J.K. (2022) ¹H, ¹⁵N and ¹³C backbone resonance assignments of the acidic domain of the human MDMX protein. Biomol NMR Assign. 16:171-178. [PubMed] [Article]
4. Pandey, A., LeBlanc, D.M., Parmar, H.B., Phạm, T.T.T., Sarker, M., Xu, L., Duncan, R., Liu, X-Q. and Rainey, J.K., (2019) Structure, amphipathy, and topology of the membrane-proximal helix 8 influence apelin receptor plasma membrane localization Biochim Biophys Acta - Biomembranes 1861:180036 [PubMed] [Article]
5. Xu, L., Weatherbee-Martin, N., Liu, X-Q. and Rainey, J.K., (2019) Recombinant silk fiber properties correlate to prefibrillar self-assembly Small 15:1805294 [PubMed] [Article]
6. Xu, L., Lefèvre, T., Orrell, K.E., Meng, Q., Auger, M., Liu, X-Q. and Rainey, J.K., (2017) Structural and mechanical roles for the C-terminal non-repetitive domain become apparent in recombinant spider aciniform silk. Biomacromolecules 18:3678-3686 [PubMed] [Article]
7. Wen R, Liu X, and Meng Q., (2017) Characterization of full-length tubuliform spidroin gene from Araneus ventricosus. Int J Biol Macromol. In press.: [PubMed]
8. Zhang, X., Liu, X.-Q., and Meng, Q., (2017) Engineered Ssp DnaX inteins for protein splicing with flanking proline. Saudi J. Biol. Sci. In press.:
9. Lin, S., Chen, G., Liu, X., Meng, Q., (2016) Chimeric spider silk proteins mediated by intein result in artificial hybrid silks. Biopolymers 105(7):385-392 [PubMed] [Article]
10. Tremblay, M-L., Xu, L., Sarker, M., Liu, X-Q. and Rainey, J.K., (2016) Characterizing aciniform silk repetitive domain backbone dynamics and hydrodynamic modularity. Int. J. Mol. Sci. 17:E1305 [PubMed] [Article]
11. Pandey, A., Shin, K., Patterson, R.E., Liu, X-Q. and Rainey, J.K., (2016) Current strategies for protein production and purification enabling membrane protein structural biology. Biochem. Cell Biol. 94(6):507-527 [PubMed] [Article]
12. Weatherbee-Martin, N., Xu, L., Hupe, A., Kreplak, L., Fudge, D.S., Liu, X-Q. and Rainey, J.K., (2016) Identification of wet-spinning and post-spin stretching methods amenable to recombinant spider aciniform silk Biomacromolecules 17:2737-2746 [PubMed] [Article]
13. Sarker, M., Orrell, K.E., Xu, L., Tremblay, M-L., Bak, J.J., Liu, X-Q. and Rainey, J.K., (2016) Tracking transitions in spider wrapping silk conformation and dynamics by ¹⁹F nuclear magnetic resonance spectroscopy Biochemistry 55:3048–3059 [PubMed] [Article]
14. Tremblay, M-L., Xu, L., Lefèvre, T., Sarker, M., Orrell, K.E., Leclerc, J., Meng, Q., Pezolet, M., Auger, M., Liu, X-Q. and Rainey, J.K., (2015) Spider wrapping silk fiber architecture arising from its modular soluble protein precursor. Sci. Rep. 5:11502 [PubMed] [Article]
15. Dai X, Xun Q, Liu XQ, Meng Q., (2015) Cysteine-free non-canonical C-intein for versatile protein C-terminal labeling through trans-splicing. Appl Microbiol Biotechnol. 99(19):8151-61 [PubMed]
16. Dai X, Liu XQ, Meng Q., (2015) Segmental expression and C-terminal labeling of protein ERp44 through protein trans-splicing. Protein Expr Purif. 112:29-36 [PubMed]
17. Pandey, A., Sarker, M., Liu, X-Q. and Rainey, J.K., (2014) Small expression tags enhance bacterial expression of the first three transmembrane segments of the apelin receptor. Biochem Cell Biol 92:269-278 [PubMed] [Article]
18. Lin Y, Li M, Song H, Xu L, Meng Q, Liu XQ., (2013) Protein trans-splicing of multiple atypical split inteins engineered from natural inteins. PLoS One 8(4):e59516 [PubMed]
19. Xu, L., Tremblay, M-L., Orrell, K.E., Leclerc, J., Meng, Q., Liu, X-Q. and Rainey, J.K., (2013) Nanoparticle self-assembly by a highly stable recombinant spider wrapping silk protein subunit. FEBS Lett 587:3273-3280 [PubMed] [Article]
20. Shin, K., Pandey, A., Liu, X-Q., Anini, Y. and Rainey, J.K., (2013) Preferential apelin-13 production by the proprotein convertase PCSK3 is implicated in obesity. FEBS Open Bio. 3:328-333 [PubMed] [Article]
21. Xu, L., Rainey, J.K., Meng, Q. and Liu, X-Q. , (2012) Recombinant minimalist spider wrapping silk proteins capable of native-like fiber formation. PLOS ONE 7:e50227 [PubMed]
22. Volkmann G, Volkmann V, Liu X.-Q., (2012) Site-specific protein cleavage in vivo by an intein-derived protease. FEBS Lett. 586:79-84 [PubMed]
23. Xu, L.*, Tremblay, M-L.*, Meng, Q., Liu, X-Q. and Rainey, J.K. (* contributed equally), (2012) ¹H, ¹³C and ¹⁵N NMR assignments of the aciniform spidroin (AcSp1) repetitive domain of Argiope trifasciata wrapping silk. Biomol. NMR Assign. 6:147-151 [PubMed]
24. Song, H., Meng, Q., and Liu, X.-Q., (2012) Protein trans-splicing of an atypical split intein showing structural flexibility and cross-reactivity. PLoS One 7(9):e45355 [PubMed]
25. Chen G, Liu X, Zhang Y, Lin S, Yang Z, Johansson J, Rising A, Meng Q., (2012) Full-length minor ampullate spidroin gene sequence. PLoS One 7(12):e52293 [PubMed]
26. Theodoro, R.C., Volkmann, G., Liu, X.-Q., and Bagagli, E., (2011) PRP8 intein in Ajellomycetaceae family pathogens: sequence analysis, splicing evaluation and homing endonuclease activity. Fungal Genetics and Biology 48:80-91 [PubMed]
27. Qi X, Wang J, Meng Q, Liu XQ, (2011) Alternative Nucleophilic Residues in Intein Catalysis of Protein Splicing. Protein Pept. Lett. 18:1226-1232 [PubMed]
28. Qi X, Meng Q, Liu X.-Q., (2011) Spontaneous C-cleavage of a mini-intein without its conserved N-terminal motif A. FEBS Lett. 585(15):2513-2518 [PubMed]
29. Volkmann G, Liu X.-Q., (2011) Intein lacking conserved C-terminal motif G retains controllable N-cleavage activity. FEBS J. 278(18):3431-3446 [PubMed]
30. Appleby-Tagoe, J.H., Thiel, I.V., Wang, Y., Wang, Y., Mootz, H.D. and Liu, X.-Q., (2011) Highly efficient and more general cis- and trans-splicing inteins through sequential directed evolution. J. Biol. Chem. 286(39):34440-34447 [PubMed]
31. Volkmann G, Murphy P.W., Rowland E.E., Cronan J.E. Jr, Liu X.Q., Blouin C, Byers D.M., (2010) Intein-mediated cyclization of bacterial acyl carrier protein stabilizes its folded conformation but does not abolish function. J Biol Chem. 285:8605-8614 [PubMed]
32. Appleby, J.H., Zhou, K., Volkmann, G., and Liu, X.-Q., (2009) Novel split intein for trans-splicing synthetic peptide onto C-terminus of protein. J. Biol. Chem. 284:6194-6199 [PubMed]
33. Volkmann, G., Sun, W., and Liu, P. X.-Q., (2009) Controllable protein cleavages through intein fragment complementation. Protein Sci. 18:2393-2402 [PubMed]
34. Volkmann, G. and Liu, P. X.-Q., (2009) Protein C-terminal labeling and biotinylation using synthetic peptide and split-intein. PLoS ONE 4(12):e8381 [PubMed]
35. Li, J., Sun, W., Wang, B., Xiao, X. and Liu, X.-Q., (2008) Protein trans-splicing as a means for viral vector-mediated in vivo gene therapy. Human Gene Therapy 19:958-964 [PubMed]
36. Meng, Q., Zhang Y., and Liu, X.-Q., (2007) Rare group I intron with insertion sequence element in a bacterial ribonucleotide reductase gene. J. Bacteriol. 189:2150-2154 [PubMed]
37. Meng, Q. Wang, Y. Liu, P. X.-Q., (2005) An intron-encoded protein assists RNA splicing of multiple similar introns of different genes. J Biol Chem. 280:35085-35088 [PubMed]
38. Yang, J., Meng, Q., and Liu, X.-Q., (2004) Intein harboring large tandem repeats in replicative DNA helicase of Trichodesmium erythraeum. Mol. Microbiol. 51:1185-1192 [PubMed]
39. Sun, W. Yang, J. Liu, X.-Q., (2004) Synthetic two-piece and three-piece split inteins for protein trans-splicing. J. Biol. Chem. 279:35281-35286 [PubMed]
40. Liu, X.-Q. and Yang, J., (2004) Prp8 intein in fungal pathogens: target for potential antifungal drugs. FEBS Lett. 572:46-50 [PubMed]
41. Liu, X.-Q. and Yang, J., (2004) Bacterial thymidylate synthase with intein, group II intron, and distinctive ThyX motifs. J. Bacteriol. 186:6316-6319 [PubMed]
42. Liu, X.-Q., Yang, J., and Meng, Q., (2003) Four inteins and three group II introns encoded in a bacterial ribonucleotide reductase gene. J. Biol. Chem. 278:46826-46831 [PubMed]
43. Liu, X.-Q. and Yang, J., (2003) Split dnaE genes encoding multiple novel inteins in Trichodesmium erythraeum. J. Biol. Chem. 278:26315-26318 [PubMed]
44. Liu, X.-Q., (2000) Protein-splicing intein: genetic mobility, origin, and evolution. Ann. Rev. Genet. 34:61-76 [PubMed]
45. Evans, Jr., T.C., Martin, D., Lolly, R., Panne, D., Sun, L., Ghosh, I., Chen, L., Benner, J., Liu, X.-Q., Xu, M.-Q., (2000) Protein trans-splicing and cyclization by naturally split intein from the dnaE gene of Synechocystis species PCC6803. J. Biol. Chem. 275:9091-9094 [PubMed]
46. Wu, H., Hu, Z., and Liu, X.-Q., (1998) Protein trans-splicing by a split intein encoded in a split DnaE gene of Synechocystis sp. PCC6803. Proc. Natl. Acad. Sci. USA 95:9226-9231 [PubMed]