Topological Twists in Nature. Issue 6 (June 2021)

• Record Type: Journal Article
• Authors: Simien, Jennifer Michelle; Haglund, Ellinor
• Is Part Of: Trends in biochemical sciences. Volume 46:Issue 6(2021)
• Page Start: 461
• Page End: 471
• Publication Date: 2021-06
• Subjects: Pierced Lasso Topology -- protein topology -- disulfide bonds -- cysteines -- molecular switches; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2020.12.004
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : The first entangled protein was observed about 30 years ago, resulting in an increased interest for uncovering the biological functions and biophysical properties of these complex topologies. Recently, the Pierced Lasso Topology (PLT) was discovered in which a covalent bond forms an intramolecular loop, leaving one or both termini free to pierce the loop. This topology is related to knots and other entanglements. PLTs exist in many well-researched systems where the PLTs have previously been unnoticed. PLTs represents 18% of all disulfide containing proteins across all kingdoms of life. In this review, we investigate the biological implications of this specific topology in which the PLT-forming disulfide may act as a molecular switch for protein function and consequently human health. Highlights: The existence of PLTs in well-established systems is often neglected with the understated role of covalent loops; many PLTs are introduced with disulfides which are highly regulated within the cell. Most PLTs are threaded topologies with a disulfide-linked loop through which the free terminus is threaded; this threaded topology introduces a new dimension to the role of disulfides in proteins and activity regulation. The association between disulfides, PLTs, and biological function may not be a stochastic event in evolution, but introduction of a new function. PLTs are found in 18% of proteins with a disulfide bond, performing a variety of biological functions that can be separated into 14 classifications. This new area of research requires attention from proteins with a disulfide to understand the correlation between the threaded topology and biological function.