Recognition motifs for importin 4 [(L)PPRS(G/P)P] and importin 5 [KP(K/ Y)LV] binding, identified by bio-informatic simulation and experimental in vitro validation

Nuclear translocation of large proteins is mediated through karyopherins, carrier proteins recognizing specific motifs of cargo proteins, known as nuclear localization signals (NLS). However, only few NLS signals have been reported until now. In the present work, NLS signals for Importins 4 and 5 were identified through an unsupervised in silico approach, followed by experimental in vitro validation. The sequences LPPRS(G/P)P and KP(K/Y)LV were identified and are proposed as recognition motifs for Importins 4 and 5 binding, respectively. They are involved in the trafficking of important proteins into the nucleus. These sequences were validated in the breast cancer cell line T47D, which expresses both Importins 4 and 5. Elucidating the complex relationships of the nuclear transporters and their cargo proteins is very important in better understanding the mechanism of nuclear transport of proteins and laying the foundation for the development of novel therapeutics, targeting specific importins. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

In this study, the nuclear localization signals (NLS) for Importins 4 and 5 were identified and validated. The sequences LPPRS(G/P)P and KP(K/Y)LV were found to be recognition motifs for Importins 4 and 5 binding, respectively. These NLS signals are involved in the nuclear transport of important proteins.