Abstract
Recently, we proposed a new strategy to construct artificial plant protein assemblies, which were induced by adding a small molecule, based on dual supramolecular interactions. In this paper, we further explored this method by employing Human Galectin-1 (Gal-1) as a building block to form self-assembled microribbons. Two non-covalent interactions, including lactose–lectin binding and dimerization of Rhodamine B (RhB), induced by the small molecule ligand addition, were involved in the crosslinking of the animal protein, resulting in the formation of assemblies. By using transmission electron microscopy (TEM), cryo-electron microscopy (cryo-EM), and three-dimensional (3D) tomographic analysis, we arrived at a possible mechanistic model for the microribbon formation. Furthermore, the morphology of protein assemblies could be fine-tuned by varying the incubation time, the protein/ligand ratio, and the chemical structures of ligands. Interestingly, the formation of protein microribbons successfully inhibited Gal-1 induced T-cell agglutination and apoptosis. This is because the multivalent and dynamic interactions in protein assemblies compete with the binding between Gal-1 and the glycans on cell surfaces, which suppresses the function of Gal-1 in promotion of tumor progression and metastasis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Fotin, A.; Cheng, Y. F.; Sliz, P.; Grigorieff, N.; Harrison, S. C.; Kirchhausen, T.; Walz, T. Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 2004, 432, 573–579.
Pollard, T. D.; Cooper, J. A. Actin, a central player in cell shape and movement. Science 2009, 326, 1208–1212.
Sára, M.; Sleytr, U. B. S-Layer proteins. J. Bacteriol. 2000, 182, 859–868.
Garcia-Seisdedos, H.; Empereur-Mot, C.; Elad, N.; Levy, E. D. Proteins evolve on the edge of supramolecular selfassembly. Nature 2017, 548, 244–247.
Luo, Q.; Hou, C. X.; Bai, Y. S.; Wang, R. B.; Liu, J. Q. Protein assembly: Versatile approaches to construct highly ordered nanostructures. Chem. Rev. 2016, 116, 13571–13632.
Bai, Y. S.; Luo, Q.; Liu, J. Q. Protein self-assembly via supramolecular strategies. Chem. Soc. Rev. 2016, 45, 2756–2767.
Sinclair, J. C. Self-assembly: Proteins on parade. Nat. Chem. 2012, 4, 346–347.
Brodin, J. D.; Smith, S. J.; Carr, J. R.; Tezcan, F. A. Designed, helical protein nanotubes with variable diameters from a single building block. J. Am. Chem. Soc. 2015, 137, 10468–10471.
Hou, C. X.; Li, J. X.; Zhao, L. L.; Zhang, W.; Luo, Q.; Dong, Z. Y.; Xu, J. Y.; Liu, J. Q. Construction of protein nanowires through cucurbit[8]uril-based highly specific host-guest interactions: An approach to the assembly of functional proteins. Angew. Chem., Int. Ed. 2013, 52, 5590–5593.
Nguyen, H. D.; Dang, D. T.; van Dongen, J. L. J.; Brunsveld, L. Protein dimerization induced by supramolecular interactions with cucurbit[8]uril. Angew. Chem., Int. Ed. 2010, 49, 895–898.
Oohora, K.; Burazerovic, S.; Onoda, A.; Wilson, Y. M.; Ward, T. R.; Hayashi, T. Chemically programmed supramolecular assembly of hemoprotein and streptavidin with alternating alignment. Angew. Chem., Int. Ed. 2012, 51, 3818–3821.
Matsunaga, R.; Yanaka, S.; Nagatoishi, S.; Tsumoto, K. Hyperthin nanochains composed of self-polymerizing protein shackles. Nat. Commun. 2013, 4, 2211.
Zhang, W.; Luo, Q.; Miao, L.; Hou, C. X.; Bai, Y. S.; Dong, Z. Y.; Xu, J. Y.; Liu, J. Q. Self-assembly of glutathione S-transferase into nanowires. Nanoscale 2012, 4, 5847–5851.
Staples, J. K.; Oshaben, K. M.; Horne, W. S. A modular synthetic platform for the construction of protein-based supramolecular polymers via coiled-coil self-assembly. Chem. Sci. 2012, 3, 3387–3392.
Sakai, F.; Yang, G.; Weiss, M. S.; Liu, Y. J.; Chen, G. S.; Jiang, M. Protein crystalline frameworks with controllable interpenetration directed by dual supramolecular interactions. Nat. Commun. 2014, 5, 4634.
Yang, G.; Zhang, X.; Kochovski, Z.; Zhang, Y. F.; Dai, B.; Sakai, F.; Jiang, L.; Lu, Y.; Ballauff, M.; Li, X. M.; Liu, C.; Chen, G. S.; Jiang, M. Precise and reversible proteinmicrotubule-like structure with helicity driven by dual supramolecular interactions. J. Am. Chem. Soc. 2016, 138, 1932–1937.
Yang, G.; Ding, H. M.; Kochovski, Z.; Hu, R. T.; Lu, Y.; Ma, Y. Q.; Chen, G. S.; Jiang, M. Highly ordered selfassembly of native proteins into 1D, 2D, and 3D structures modulated by the tether length of assembly-inducing ligands. Angew. Chem., Int. Ed. 2017, 56, 10691–10695.
Rabinovich, G. A.; Toscano, M. A. Turning “sweet” on immunity: Galectin-glycan interactions in immune tolerance and inflammation. Nat. Rev. Immunol. 2009, 9, 338–352.
Argüeso, P.; Panjwani, N. Focus on molecules: Galectin-3. Exp. Eye. Res. 2011, 92, 2–3.
Perillo, N. L.; Pace, K. E.; Seilhamer, J. J.; Baum, L. G. Apoptosis of T cells mediated by galectin-1. Nature 1995, 378, 736–739.
He, J. L.; Baum, L. G. Endothelial cell expression of galectin-1 induced by prostate cancer cells inhibits T-cell transendothelial migration. Lab. Invest. 2006, 86, 578–590.
Tribulatti, M. V.; Figini, M. G.; Carabelli, J.; Cattaneo, V.; Campetella, O. Redundant and antagonistic functions of galectin-1, -3, and -8 in the elicitation of T cell responses. J. Immunol. 2012, 188, 2991–2999.
Disney, M. D.; Childs-Disney, J. L. "Supra"molecular recognition of galectin 1. Chem. Biol. 2007, 14, 1095–1097.
Thiemann, S.; Baum, L. G. Galectins and immune responses—Just how do they do those things they do? Annu. Rev. Immunol. 2016, 34, 243–264.
Nesmelova, I. V.; Ermakova, E.; Daragan, V. A.; Pang, M.; Menéndez, M.; Lagartera, L.; Solís, D.; Baum, L. G.; Mayo, K. H. Lactose binding to galectin-1 modulates structural dynamics, increases conformational entropy, and occurs with apparent negative cooperativity. J. Mol. Biol. 2010, 397, 1209–1230.
López-Lucendo, M. F.; Solís, D.; André, S.; Hirabayashi, J.; Kasai, K. I.; Kaltner, H.; Gabius, H. J.; Romero, A. Growthregulatory human galectin-1: Crystallographic characterisation of the structural changes induced by single-site mutations and their impact on the thermodynamics of ligand binding. J. Mol. Biol. 2004, 343, 957–970.
Belitsky, J. M.; Nelson, A.; Hernandez, J. D.; Baum, L. G.; Stoddart, J. F. Multivalent interactions between lectins and supramolecular complexes: Galectin-1 and self-assembled pseudopolyrotaxanes. Chem. Biol. 2007, 14, 1140–1151.
Grishagin, I. V. Automatic cell counting with ImageJ. Anal. Biochem. 2015, 473, 63–65.
Acknowledgements
We acknowledge the financial support from the National Natural Science Foundation of China (Nos. 51721002, 21504016, and 91527305). We thank Joint Lab for Structural Research at the Integrative Research Institute for the Sciences (IRIS Adlershof, Berlin) for Cryo-TEM imaging.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Qi, W., Zhang, Y., Kochovski, Z. et al. Self-assembly of Human Galectin-1 via dual supramolecular interactions and its inhibition of T-cell agglutination and apoptosis. Nano Res. 11, 5566–5572 (2018). https://doi.org/10.1007/s12274-018-2169-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12274-018-2169-7