The N-end Rule Pathway: Molecular Principles of Structural Recognition and Rational Design Opportunities
Year: 2012
Type: article
Abstract: The N-end rule relates the regulation of the in vivo half-life of a protein to the identity of its N-terminal residue. A set of N-terminal degradation signals is targeted by the recognition components (N-recognins) of the N-end rule pathway. Recent reports on the N-end rule substrates, components, functions and structural basis of substrate recognition have provided critical insights. The N-end rule pathway is now emerging as a major ubiquitin-dependent cellular proteolytic system. The scope of this dissertation is to understand the structural principles of substrate recognition and utilize this structural basis to provide insights on the functions and underlying mechanisms of the N-end rule pathway. We were also interested in exploring the N-end rule pathway as an intracellular target for heterodivalent interactions. We discuss and demonstrate the basis of thermodynamics and kinetics principles that govern these interactions between the N-recognins and the heterodivalent ligands. We further pursued to exploit these principles in the design and development of high affinity ligands that target the N-end rule pathway.
Author: Shashi Sriram
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2215562240