Evolutionarily Conserved Sequence Features Regulate the Formation of the FG Network at the Center of the Nuclear Pore Complex.

M Peyro,B.L Lee,M.R.K Mofrad,M Soheilypour

doi:10.1038/srep15795

Abstract

The nuclear pore complex (NPC) is the portal for bidirectional transportation of cargos between the nucleus and the cytoplasm. While most of the structural elements of the NPC, i.e. nucleoporins (Nups), are well characterized, the exact transport mechanism is still under much debate. Many of the functional Nups are rich in phenylalanine-glycine (FG) repeats and are believed to play the key role in nucleocytoplasmic transport. We present a bioinformatics study conducted on more than a thousand FG Nups across 252 species. Our results reveal the regulatory role of polar residues and specific sequences of charged residues, named ‘like charge regions’ (LCRs), in the formation of the FG network at the center of the NPC. Positively charged LCRs prepare the environment for negatively charged cargo complexes and regulate the size of the FG network. The low number density of charged residues in these regions prevents FG domains from forming a relaxed coil structure. Our results highlight the significant role of polar interactions in FG network formation at the center of the NPC and demonstrate that the specific localization of LCRs, FG motifs, charged, and polar residues regulate the formation of the FG network at the center of the NPC.

Highlights

The nuclear pore complex (NPC) is the sole gateway for bidirectional transport of cargo between the cytoplasm and nucleus[1]
Zhao et al investigated the interaction of CRM1 with Tpr, a nuclear pore protein located inside the nuclear basket, and identified nine possible binding sites for Tpr on CRM113
Ghavami et al investigated the distribution of FG Nups in the channel by means of a high resolution coarse-grained molecular dynamics model and showed that the distribution is encoded in the sequences of FG Nups[19]

Summary

Introduction

The nuclear pore complex (NPC) is the sole gateway for bidirectional transport of cargo between the cytoplasm and nucleus[1]. Using a coarse-grained model, Ando et al.[18] performed a comprehensive study on the effect of the sequence on the morphology of single FG Nups and grafted rings of FG Nups. Mincer and Simon used the pairwise agent interaction with rational superpositions (PAIRS) model to predict factors such as the bimodal cargo distribution, the effect of the number of NLS tags and RanGTP gradient[21] They modeled rings of Nups and the NPC as a whole and verified their model using a variety of experimental data. Azimi et al further extended their ABM model to study the dynamics of mRNA export through the nuclear pore[28] These studies shed light on the behavior of specific domains of FG Nups, further examinations are needed to capture a comprehensive picture of the overall characteristics, behavior and function of Nups inside the NPC. Our approach is verified by comparing the results against available data[5,18,19,39]

Methods

Results

Conclusion