Proteins' Knotty Problems. Issue 2 (18th January 2019)

• Record Type: Journal Article
• Authors: Jarmolinska, Aleksandra I.; Perlinska, Agata P.; Runkel, Robert; Trefz, Benjamin; Ginn, Helen M.; Virnau, Peter; Sulkowska, Joanna I.
• Is Part Of: Journal of molecular biology. Volume 431:Issue 2(2019)
• Page Start: 244
• Page End: 257
• Publication Date: 2019-01-18
• Subjects: knotted proteins -- folding; Aifm1 apoptosis-inducing factor 1 -- CTD C-terminal domain -- CaCA Ca2+/cation -- CAX H+/Ca2+ exchanger -- NCX Na+/Ca2+ exchanger -- RHH ribbon–helix–helix; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.10.012
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Knots in proteins are increasingly being recognized as an important structural concept, and the folding of these peculiar structures still poses considerable challenges. From a functional point of view, most protein knots discovered so far are either enzymes or DNA-binding proteins. Our comprehensive topological analysis of the Protein Data Bank reveals several novel structures including knotted mitochondrial proteins and the most deeply embedded protein knot discovered so far. For the latter, we propose a novel folding pathway based on the idea that a loose knot forms at a terminus and slides to its native position. For the mitochondrial proteins, we discuss the folding problem from the perspective of transport and suggest that they fold inside the mitochondria. We also discuss the evolutionary origin of a novel class of knotted membrane proteins and argue that a novel knotted DNA-binding protein constitutes a new fold. Finally, we have also discovered a knot in an artificially designed protein structure. Graphical Abstract: Unlabelled Image Highlights: We considerably expand the number of known knotted proteins and discover among others the first knotted mitochondrial and membrane proteins. We suggest folding pathways for these peculiar structures based on numerical simulations.