Structural and oxygen binding properties of dimeric horse myoglobin.
Abstract: Myoglobin (Mb) stores dioxygen in muscles, and is a fundamental model protein widely used in molecular design. The presence of dimeric Mb has been known for more than forty years, but its structural and oxygen binding properties remain unknown. From an X-ray crystallographic analysis at 1.05 Å resolution, we found that dimeric metMb exhibits a domain-swapped structure with two extended α-helices. Each new long α-helix is formed by the E and F helices and the EF-loop of the original monomer, and as a result the proximal and distal histidines of the heme originate from different protomers. The heme orientation in the dimer was in the normal mode as in the monomer, but regulated faster from the reverse to normal orientation. The dimer possessed the oxygen binding property, although it exhibited a slightly higher oxygen binding affinity (∼1.4 fold) compared to the monomer and showed no cooperativity for oxygen binding. The oxygen binding rate constant (k(on)) of the dimer ((14.0 ± 0.7) × 10(6) M(-1) s(-1)) was similar to that of the monomer, whereas the oxygen dissociation rate constant (k(off)) of the dimer (8 ± 1 s(-1)) was smaller than that of the monomer (12 ± 1 s(-1)). We attribute the similar k(on) values to their active site structures being similar, whereas the faster regulation of the heme orientation and the smaller k(off) in the dimer are presumably due to the slight change in the active site structure and/or more rigid structure compared to the monomer. These results show that domain swapping may be a new tool for protein engineering.
Publication Date: 2012-08-13 PubMed ID: 22885714DOI: 10.1039/c2dt30893bGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines the structural and oxygen binding properties of dimeric horse myoglobin, a protein that stores oxygen in muscles. The study reveals new insights about the modified functionality of this biologically significant protein when in its dimeric form.
Structure of Dimeric Myoglobin
- The researchers performed an X-ray crystallographic analysis at 1.05 Å resolution to understand the structure of dimeric myoglobin.
- The dimeric form of myoglobin was found to exhibit a domain-swapped structure with two extended α-helices each formed by the E and F helices and the EF-loop of the original monomer (single unit).
- In this structure, the heme chemical group (that helps bind oxygen to the protein), had the proximal and distal histidines (important sites for binding) that originated from different protomers (individual units within the dimer).
Oxygen Binding in Dimeric Myoglobin
- The heme orientation (the arrangement of the heme group) in the dimeric myoglobin remained the same as in its monomeric form, suggesting that the basic functionality of this protein to bind oxygen isn’t significantly altered.
- However, the dimer exhibited a slightly higher oxygen binding affinity, which is about 1.4 times greater than the monomer. Additionally, the dimer showed a lack of cooperative binding, meaning oxygen binding in one active site does not influence the oxygen binding in the other site.
Oxygen Binding and Dissociation Rate Constants
- The rate constant for oxygen binding (k(on)) was found to be similar for both the dimer and monomer forms, which indicates that their active site structures are comparable.
- However, the rate at which oxygen dissociated (k(off)) from the dimer was lower than the dissociation rate in the monomer, thus showing a variation in their oxygen release properties. This is linked to a possible slight change in the active site structure and/or a more rigid structure in the dimer.
Implications of Findings
- This variation in the properties highlights a potential for the use of domain swapping as a tool in protein engineering. For instance, creating dimeric forms of a protein could alter characteristics such as affinity and dissociation rates, which could be beneficial in applied biology and medicine.
Cite This Article
APA
Nagao S, Osuka H, Yamada T, Uni T, Shomura Y, Imai K, Higuchi Y, Hirota S.
(2012).
Structural and oxygen binding properties of dimeric horse myoglobin.
Dalton Trans, 41(37), 11378-11385.
https://doi.org/10.1039/c2dt30893b Publication
Researcher Affiliations
- Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5, Takayama, Ikoma, Nara 630-0192, Japan.
MeSH Terms
- Animals
- Circular Dichroism
- Crystallography, X-Ray
- Dimerization
- Horses
- Magnetic Resonance Spectroscopy
- Models, Molecular
- Myoglobin / chemistry
- Myoglobin / metabolism
- Oxygen / chemistry
- Oxygen / metabolism
Citations
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