Role of Zero-Order Loop in Protein Unfolding Case Study with Apoazurin
Paper in proceedings, 2020

Pseudomonas aeruginosa apoazurin (apo, without the copper cofactor) is a two-state folder that has a single disulfide bond between residues 3 and 26. This bond covalently connects the N-termini of beta-strands 1 and 3; thereby it creates a zero-order loop. The loop restricts the conformational space for the apoazurin polypeptide. In order to understand the role played by the zero-order loop, we used molecular dynamics (MD) simulations to compare two variants of apoazurin; one variant called “loop” which contained the disulfide and another called “open” in which the disulfide bond between residues 3 and 26 was removed. MD simulations were performed to probe the unfolding pathway and stability of the two apoazurin variants at different urea concentrations and temperatures. Our results show that the folded structure apoazurin is somewhat more stable due to the presence of the disulfide bond. However, the disulfide bond plays a prominent role in the apoazurin unfolding mechanism: we find that it changes both the folding-transition state and the unfolded-state ensemble of conformations.

Apoazurin

zero-order loop

Author

Dirar M. Homouz

Khalifa University

University of Houston

Fabio Zegarra

University of Houston

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Margaret S. Cheung

Rice University

University of Houston

Biophysical Journal

0006-3495 (ISSN) 1542-0086 (eISSN)

Vol. 118 3, Supplement 1 197A-197A

64th Annual Meeting of the Biophysical-Society
San Diego, USA,

Subject Categories

Physiology

Other Physics Topics

Biophysics

DOI

10.1016/j.bpj.2019.11.1191

More information

Latest update

6/12/2020