Working from distance: engineering allosteric control on PDZ3 domain selectivity from ZO-1 protein through chimera domain fusion
- Project Identification
- Project Period
- 1/2019 - 12/2021
- Investor / Pogramme / Project type
- Czech Science Foundation
- MU Faculty or unit
- Central European Institute of Technology
- Cooperating Organization
Institute of Organic Chemistry and Biochemistry of the ASCR, v. v. i.
Allosteric modulation of a protein domain function is one of the most intriguing concepts in molecular biology nowadays (Borgia et al. 2015, Ma et al. 2011, England et al. 2011). PDZ domains represent ideal candidate to decipher mechanism of binding specificity via adjacent domains synergy in multi-domain protein context by means of structural, computational and biophysical methods. Ultimate goal of this project is to understand PDZ external allostery brought by adjacent domain together with folding, structure, dynamics and binding properties of the fusion proteins. We will study molecules containing PDZ3 from ZO-1 protein (homo sapiens) in various 2 domains fusion constructs and describe the mechanism in which PDZ3 specificity is controlled by a character, position and size of the attached domain. Further, we aim to explain at which extent is the domain context the important regulatory element of PDZ domain specificity and how could be related to various ways of substrate binding.