GSBS Student Publications

Title

Insight into the allosteric mechanism of Scapharca dimeric hemoglobin

Student Author(s)

Jennifer M. Laine

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

11-25-2014

Document Type

Article

Medical Subject Headings

Allosteric Regulation; Animals; Entropy; Hemoglobins; Molecular Dynamics Simulation; Protein Binding; Protein Multimerization; Scapharca

Disciplines

Biochemistry | Biochemistry, Biophysics, and Structural Biology | Molecular Biology

Abstract

Allosteric regulation is an essential function of many proteins that control a variety of different processes such as catalysis, signal transduction, and gene regulation. Structural rearrangements have historically been considered the main means of communication between different parts of a protein. Recent studies have highlighted the importance, however, of changes in protein flexibility as an effective way to mediate allosteric communication across a protein. Scapharca dimeric hemoglobin (HbI) is the simplest possible allosteric system, with cooperative ligand binding between two identical subunits. Thermodynamic equilibrium studies of the binding of oxygen to HbI have shown that cooperativity is an entropically driven effect. The change in entropy of the system observed upon ligand binding may arise from changes in the protein, the ligand, or the water of the system. The goal of this study is to determine the contribution of the change in entropy of the protein backbone to HbI cooperative binding. Molecular dynamics simulations and nuclear magnetic resonance relaxation techniques have revealed that the fast internal motions of HbI contribute to the cooperative binding to carbon monoxide in two ways: (1) by contributing favorably to the free energy of the system and (2) by participating in the cooperative mechanism at the HbI subunit interface. The internal dynamics of the weakly cooperative HbI mutant, F97Y, were also investigated with the same methods. The changes in backbone NH dynamics observed for F97Y HbI upon ligand binding are not as large as for the wild type, in agreement with the reduced cooperativity observed for this mutant. The results of this study indicate that interface flexibility and backbone conformational entropy of HbI participate in and are important for the cooperative mechanism of carbon monoxide binding.

Rights and Permissions

Citation: Biochemistry. 2014 Nov 25;53(46):7199-210. doi: 10.1021/bi500591s. Epub 2014 Nov 14. Link to article on publisher's site

DOI of Published Version

10.1021/bi500591s

Related Resources

Link to Article in PubMed

Journal Title

Biochemistry

PubMed ID

25356908