Issue 59, 2021, Issue in Progress

Experimental and theoretical study on converting myoglobin into a stable domain-swapped dimer by utilizing a tight hydrogen bond network at the hinge region

Abstract

Various factors, such as helical propensity and hydrogen bonds, control protein structures. A frequently used model protein, myoglobin (Mb), can perform 3D domain swapping, in which the loop at the hinge region is converted to a helical structure in the dimer. We have previously succeeded in obtaining monomer–dimer equilibrium in the native state by introducing a high α-helical propensity residue, Ala, to the hinge region. In this study, we focused on another factor that governs the protein structure, hydrogen bonding. X-ray crystal structures and thermodynamic studies showed that the myoglobin dimer was stabilized over the monomer when keeping His82 to interact with Lys79 and Asp141 through water moleclues and mutating Leu137, which was located close to the H-bond network at the dimer hinge region, to a hydrophilic amino acid (Glu or Asp). Molecular dynamics simulation studies confirmed that the number of H-bonds increased and the α-helices at the hinge region became more rigid for mutants with a tighter H-bond network, supporting the hypothesis that the myoglobin dimer is stabilized when the H-bond network at the hinge region is enhanced. This demonstrates the importance and utility of hydrogen bonds for designing a protein dimer from its monomer with 3D domain swapping.

Graphical abstract: Experimental and theoretical study on converting myoglobin into a stable domain-swapped dimer by utilizing a tight hydrogen bond network at the hinge region

Supplementary files

Article information

Article type
Paper
Submitted
14 Sep 2021
Accepted
12 Nov 2021
First published
23 Nov 2021
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2021,11, 37604-37611

Experimental and theoretical study on converting myoglobin into a stable domain-swapped dimer by utilizing a tight hydrogen bond network at the hinge region

C. Xie, H. Shimoyama, M. Yamanaka, S. Nagao, H. Komori, N. Shibata, Y. Higuchi, Y. Shigeta and S. Hirota, RSC Adv., 2021, 11, 37604 DOI: 10.1039/D1RA06888A

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