Heterogeneous side chain conformation highlights a network of interactions implicated in hysteresis of the knotted protein, minimal tied trefoil. (20th August 2015)

• Record Type: Journal Article
• Authors: Burban, David J; Haglund, Ellinor; Capraro, Dominique T; Jennings, Patricia A
• Is Part Of: Journal of physics. Volume 27:Number 35(2015)
• Publication Date: 2015-08-20
• Subjects: trefoil knot -- hysteresis -- SPOUT methyltransferase -- 1O6D -- minimal tied trefoil Thermotoga maritma; Condensed matter -- Periodicals; Matière condensée -- Périodiques; Vaste stoffen; Vloeistoffen; Natuurkunde; Electronic journals; Computer network resources; 530.4105
• DOI: 10.1088/0953-8984/27/35/354108
• Languages: English
• ISSNs: 0953-8984

Abstract

Abstract: Hysteresis is a signature for a bistability in the native landscape of a protein with significant transition state barriers for the interconversion of stable species. Large global stability, as in GFP, contributes to the observation of this rare hysteretic phenomenon in folding. The signature for such behavior is non-coincidence in the unfolding and refolding transitions, despite waiting significantly longer than the time necessary for complete denaturation. Our work indicates that hysteresis in the knotted protein, the minimal tied trefoil from Thermotoga maritma (MTT Tm ), is mediated by a network of side chain interactions within a tightly packed core. These initially identified interactions include proline 62 from a tight β -like turn, phenylalanine 65 at the beginning of the knotting loop, and histidine 114 that initiates the threading element. It is this tightly packed region and the knotting element that we propose is disrupted with prolonged incubation in the denatured state, and is involved in the observed hysteresis. Interestingly, the disruption is not linked to backbone interactions, but rather to the packing of side chains in this critical region.