Journal of Proteomics & Bioinformatics
Open Access

Elucidation, functional clustering and structural characterization of βTrCP1 substrates through a molecular dynamics study

13^th International Conference on Structural and Molecular Biology: Techniques & Market Analysis

October 22-23, 2018 | Ottawa, Canada

Sajid Rashid, Shagufta Shafique, Saima Younis and Hafsa Niaz

Quaid-i-Azam University, Pakistan

Posters & Accepted Abstracts: J Proteomics Bioinform

Abstract :

The current interest in the identification and characterization of βTrCP1 substrates necessitates a promising approach with broad structural constraints of WD40 potential binding sites. Here, we employed an in silico integrative approach to identify putative novel substrates of βTrCP1. Through a screened degradation motif (DSGXXS) for the entire human proteome and comparative substrate binding analysis of βTrCP1, we identified 344 substrates, sharing high sequence similarity with the consensus motif. Subsequent filtering on the basis of functional annotation and clustering resulted in of hits having clear roles in various cancer types. These substrates were phosphorylated at the Ser residues (Ser14 and Ser18) of the conserved motif. A comprehensive and thorough analysis of βTrCP1â??phosphopeptide association indicated residual contributions located at the upper face of the b-propeller. Evidently, upon binding to phosphopeptides, the channel of βTrCP1 more open conformation to assist substrate binding. To elaborate on the oncogenic function of βTrCP1, the SKP1â??βTrCP1â??CDH6 ternary complex was docked against CUL1â??RBX1 and the acquired model exactly resembled the previously characterized SKP1â??βTrCP1â?? β-catenin model. Overall, a deeper understanding of substrate targeting mechanisms coupled with the structural knowledge of βTrCP1 and associated proteins will be useful for designing novel targets for cancer therapeutics.

Biography :

E-mail: sajid@qau.edu.pk