Liu, Paul Xiang-Qin - Dalhousie University - Department of Biochemistry & Molecular Biology

研究领域

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.

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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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] 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] Volkmann, G., Sun, W., and Liu, P. X.-Q., (2009) Controllable protein cleavages through intein fragment complementation. Protein Sci. 18:2393-2402 [PubMed]