A Structural Proteomics Exploration of Formation of Cohesin Complex to Help Unearthing Chromosomal Activities

Cohesin complex is commonly known to have various important roles in maintaining chromosome stability, cell division, DNA-repair and also in epigenetic regulation. It consists of four major proteins, namely, SMC3, SMC1A, RAD21 and SA-1/SA-2, which are responsible for its dynamic structure and function. Mutations in the subunits of cohesin can lead to various developmental disorders and even cancer. In spite of many research efforts, both experimental and theoretical, there still remains a knowledge gap in deciphering the structure and function of this complex. In light of this, this work is devoted in developing the pipelines based on structural proteomics to deduce the structure of the cohesin complex and to validate the same. The semiautomatic pipeline to be used in this work comprises three major stages. In the first stage, the individual protein structures will be predicted by selecting the best model from those outputted by the contemporary best predictors, then validated using standard validation parameters and finally authenticated using an Experimental Information based Validation (EIbV) method compiling all the cohesin constituent protein structure information so far published. In the second stage, all possible interactions between each pair of cohesin constituent proteins will be studied to solve the complex structure by iteratively adding the proteins one after another in the complex. The final complex structure will be validated by the application of EIbV again. It will also pave the way for better understanding of its roles and functions that are of vital importance for many pathophysiological functions.