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Low‐resolution structures of modular nanotransporters shed light on their functional activity
Modular nanotransporters (MNTs) are multifunctional chimeric polypeptides for the multistep transport of locally acting cytotoxic agents into the nuclei of cancer target cells. MNTs consist of several polypeptide domains (functional modules) for the recognition of a cell‐surface internalizable recep...
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Published in: | Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2020-12, Vol.76 (12), p.1270-1279 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Modular nanotransporters (MNTs) are multifunctional chimeric polypeptides for the multistep transport of locally acting cytotoxic agents into the nuclei of cancer target cells. MNTs consist of several polypeptide domains (functional modules) for the recognition of a cell‐surface internalizable receptor, pH‐dependent endosomal escape and subsequent transport into the nucleus through the nuclear pores. MNTs are a promising means for cancer treatment. As has been shown previously, all of the modules of MNTs retain their functionalities. Despite their importance, there is no structural information available about these chimeric polypeptides, which hampers the creation of new MNT variants. Here, a low‐resolution 3D structure of an MNT is presented which was obtained by atomic force microscopy, transmission electron microscopy and small‐angle X‐ray scattering coupled to size‐exclusion chromatography. The data suggest that the MNT can adopt two main conformations, but in both conformations the protein N‐ and C‐termini are distanced and do not influence each other. The change in the MNT conformation during acidification of the medium was also studied. It was shown that the fraction of the elongated conformation increases upon acidification. The results of this work will be useful for the development of MNTs that are suitable for clinical trials and possible therapeutic applications.
Artificial multifunctional polypeptide constructs (modular nanotransporters, MNTs) have great potential in the treatment of various diseases, particularly cancer. In this study, a low‐resolution 3D structure of an MNT in solution was obtained by atomic force microscopy, transmission electron microscopy and small‐angle X‐ray scattering coupled to size‐exclusion chromatography. |
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ISSN: | 2059-7983 0907-4449 2059-7983 1399-0047 |
DOI: | 10.1107/S2059798320013765 |