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Paul Xiang-Qin Liu

PhD (Cornell)


Department member since 1989

Tupper 9-M1


Intein and Protein Splicing

Research Areas

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.

Graduate Students

Andy Song PhD

Postdoctoral Fellows

Lingling Xu Donghua University


  1. 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]
  2. 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. 147:E1305 [PubMed] [Article]
  3. 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]
  4. 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]
  5. 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 55:30483059 [PubMed] [Article]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. 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]
  25. Volkmann, G., Sun, W., and Liu, P. X.-Q., (2009) Controllable protein cleavages through intein fragment complementation. Protein Sci. 18:2393-2402 [PubMed]
  26. 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]
  27. 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]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. Liu, X.-Q. and Yang, J., (2004) Prp8 intein in fungal pathogens: target for potential antifungal drugs. FEBS Lett. 572:46-50 [PubMed]
  33. 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]
  34. 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]
  35. Liu, X.-Q. and Yang, J., (2003) Split dnaE genes encoding multiple novel inteins in Trichodesmium erythraeum. J. Biol. Chem. 278:26315-26318 [PubMed]
  36. Liu, X.-Q., (2000) Protein-splicing intein: genetic mobility, origin, and evolution. Ann. Rev. Genet. 34:61-76 [PubMed]
  37. 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]
  38. 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]