Research

Engineering Sciences

Title :

Understanding the role of polarity and charge patterning on the structure and function of Nuclear Pore Complexes (NPCs)

Area of research :

Engineering Sciences

Principal Investigator :

Dr. Mithun Radhakrishna, Indian Institute Of Technology (IIT) Gandhinagar, Gujarat

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Nuclear Pore Complexes (NPCs) are perforations in the bilayer nuclear membrane of eukaryotic cells, consisting of 30 different proteins called Nucleoporins (NUPs). NUPs contain intrinsically disordered regions (IDRs), which are challenging to quantify through traditional experimental methods. The inner pathway of NPCs is populated by FG NUPs, which contain a high proportion of amino acid residues Glycine (G) and Phenylalanine (F). Sequence analysis of NUPs reveals that the structural region forms the inner and peripheral pathway of the NPC, while the disordered region forms the inner and peripheral pathway. Within the disordered region, NUPs have collapsed and extended regions, with charged residues playing a key role in identifying these distinctions. The study aims to develop a key metric using charged residues and patterning as the identifier of the collapsed, extended, and structural region of NUPs, extending this algorithm to a wide range of other NUPs across humans and plants whose structure is yet to be quantified. The proposal aims to understand the role of polar residues in the collapsed region in regulating the transport of cargo across NPCs. The ratio of the length of the collapsed to extended regions is crucial in obtaining a pore structure and their role in regulating transport. The proposed approach could be applied to developing biocompatible synthetic membranes with high permeability and selectivity. Understanding and quantifying the role of polar and charged residues in NUPs could either develop a new metric to identify IDRs or improve existing algorithms that predict IDRs.

Total Budget (INR):

32,82,396

Organizations involved