Dataset Information

Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations.

ABSTRACT: A growing number of proteins have been identified as knotted in their native structures, with such entangled topological features being expected to play stabilizing roles maintaining both the global fold and the nature of proteins. However, the molecular mechanism underlying the stabilizing effect is ambiguous. Here, we combine unbiased and mechanical atomistic molecular dynamics simulations to investigate how a protein is stabilized by an inherent knot by directly comparing chemical, thermal, and mechanical denaturing properties of two proteins having the same sequence and secondary structures but differing in the presence or absence of an inherent knot. One protein is YbeA from Escherichia coli, containing a deep trefoil knot within the sequence, and the other is the modified protein with the knot of YbeA being removed. Under certain chemical denaturing conditions, the unknotted protein fully unfolds whereas the knotted protein does not, suggesting a higher intrinsic stability for the protein having a knot. Both proteins unfold under enhanced thermal fluctuations but at different rates and with distinct pathways. Opening the hydrophobic core via separation between two ?-helices is identified as a crucial step initiating the protein unfolding, which, however, is restrained for the knotted protein by topological and geometrical frustrations. Energy barriers for denaturing the protein are reduced by removing the knot, as evidenced by mechanical unfolding simulations. Finally, yet importantly, no obvious change in size or location of the knot was observed during denaturing processes, indicating that YbeA may remain knotted for a relatively long time during and after denaturation.

SUBMITTER: Xu Y

PROVIDER: S-EPMC6225051 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations.

Xu Yan Y Li Shixin S Yan Zengshuai Z Luo Zhen Z Ren Hao H Ge Baosheng B Huang Fang F Yue Tongtao T

Biophysical journal 20180922 9

A growing number of proteins have been identified as knotted in their native structures, with such entangled topological features being expected to play stabilizing roles maintaining both the global fold and the nature of proteins. However, the molecular mechanism underlying the stabilizing effect is ambiguous. Here, we combine unbiased and mechanical atomistic molecular dynamics simulations to investigate how a protein is stabilized by an inherent knot by directly comparing chemical, thermal, a ...[more]

PMID: 30314655

Similar Datasets

Project description:Hemoglobin is one of the most widely studied proteins genetically, biochemically, and structurally. It is an oxygen carrying tetrameric protein that imparts the characteristic red color to blood. Each chain of hemoglobin harbors a heme group embedded in a hydrophobic pocket. Several studies have investigated structural variations present in mammalian hemoglobin and their functional implications. However, camel hemoglobin has not been thoroughly explored, especially from a structural perspective. Importantly, very little is known about how the heme group interacts with hemoglobin under varying conditions of osmolarity and temperature. Several experimental studies have indicated that the tense (T) state is more stable than the relaxed (R) state of hemoglobin under normal physiological conditions. Despite the fact that R state is less stable than the T state, no extensive structural dynamics studies have been performed to investigate global quaternary transitions of R state hemoglobin under normal physiological conditions. To evaluate this, several 500 ns all-atom molecular dynamics simulations were performed to get a deeper understanding of how camel hemoglobin behaves under stress, which it is normally exposed to, when compared to human hemoglobin. Notably, camel hemoglobin was more stable under physiological stress when compared to human hemoglobin. Additionally, when compared to camel hemoglobin, cofactor-binding regions of hemoglobin also exhibited more fluctuations in human hemoglobin under the conditions studied. Several differences were observed between the residues of camel and human hemoglobin that interacted with heme. Importantly, distal residues His58 of α hemoglobin and His63 of β hemoglobin formed more sustained interactions, especially at higher temperatures, in camel hemoglobin. These residues are important for oxygen binding to hemoglobin. Thus, this work provides insights into how camel and human hemoglobin differ in their interactions under stress.

Dataset Information

Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations.

Publications

Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets