INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
artículos
Título:
Engineered chimeras reveal the structural basis of hexacoordination in globins: A case study of neuroglobin and myoglobin
Autor/es:
IGNACIO BORON; LUCIANA CAPECE; FRANCESCA PENNACCHIETTI; DIANA E. WETZLER; STEFANO BRUNO; STEFANIA ABBRUZZETTI; LUCÍA CHISARI; F. JAVIER LUQUE; CRISTIANO VIAPPIANI; MARCELO MARTÍ; DARIO ESTRÍN; ALEJANDRO NADRA
Revista:
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2015 vol. 1850 p. 169 - 169
ISSN:
0304-4165
Resumen:
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.