Related Experiment Video
Updated: Apr 20, 2026
T-wave Ion Mobility-mass Spectrometry: Basic Experimental Procedures for Protein Complex Analysis
Published on: July 31, 2010
Engineered chimeras reveal the structural basis of hexacoordination in globins: a case study of neuroglobin and
Ignacio Boron1, Luciana Capece2, Francesca Pennacchietti3
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires C1428EHA, Argentina; IQUIBICEN-CONICET, Argentina.
Background:
Myoglobin (Mb) and neuroglobin (Ngb) are representative members of pentacoordinated and bis-histidyl, hexacoordinated globins. In spite of their low sequence identity, they show surprisingly similar three-dimensional folds. The ability of Ngb to form a hexacoordinated bis-histidyl complex with the distal HisE7 has a strong impact on ligand affinity. The factors governing such different behaviors have not been completely understood yet, even though they are extremely relevant to establish structure-function relationships within the globin superfamily.
Methods:
In this work we generated chimeric proteins by swapping a previously identified regulatory segment - the CD region - and evaluated comparatively the structural and functional properties of the resulting proteins by molecular dynamics simulations, and spectroscopic and kinetic investigations.
Results:
Our results show that chimeric proteins display heme coordination properties displaced towards those expected for the corresponding CD region. In particular, in the absence of exogenous ligands, chimeric Mb is found as a partially hexacoordinated bis-histidyl species, whereas chimeric Ngb shows a lower equilibrium constant for forming a hexacoordinated bis-histidyl species.
Conclusions:
While these results confirm the regulatory role of the CD region for bis-histidyl hexacoordination, they also suggest that additional sources contribute to fine tune the equilibrium. General significance Globins constitute a ubiquitous group of heme proteins widely found in all kingdoms of life. These findings raise challenging questions regarding the structure-function relationships in these proteins, as bis-histidyl hexacoordination emerges as a novel regulatory mechanism of the physiological function of globins.
Related Concept Videos
02:42Valence Bond Theory
01:27Globular Proteins
Globular proteins serve many important physiological functions, such as acting as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be soluble in the aqueous...
02:34Structural Isomerism
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly,...
02:51Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
01:58Cooperative Allosteric Transitions
02:57Coordination Number and Geometry