GLOBIN PROTEINS:

NEUROGLOBIN
Maurizio Brunori, Beatrice Vallone, Tommaso Moschetti, Adriana E. Miele, G.U. Nienhaus (links)

Neuroglobin is expressed in vertebrates brain and belongs to a branch of the globin family that diverged early in evolution. Experiments in vivo and in vitro showed increased hypoxic stress damage upon repressing neuroglobin biosynthesis and improved recovery following overexpression.
We have solved the structure of unliganded (met) and CO-bound mouse neuroglobin. It shows internal heme hexacoordination, which controls oxygen affinity and kinetics.
Neuroglobin's structure shows a peculiar internal cavity of very large size. Binding of heme ligands is associated to a conformational change involving the heme that “slides” into the pre-existing cavity and makes the sixth coordination position available.
We have produced and crystallized several mutants of murine Neuroglobin, a protein expressed in the brain that is involved in the hypoxic stress defense mechanism. The structure of these mutants will help the elucidation of the still unknown mechanism by which protection of the nervous tissue is exerted.
We are attempting time-resolved structural studies of neuroglobin and we are also carrying out EXAFS and XANES experiment in the crystal states (in collaboration with A. Arcovito and S. Della Longa, link).



A. Unliganded and liganded structures of mouse Neuroglobin.
B. Variations in the large internal cavity upon ligand binding.

References
Brunori M, Vallone B. (2006)
A globin for the brain. FASEB J. Nov;20(13):2192-7.

Brunori M, Giuffre A, Nienhaus K, Nienhaus GU, Scandurra FM, Vallone B. (2005)
Neuroglobin, nitric oxide, and oxygen: functional pathways and conformational changes. Proc Natl Acad Sci U S A. 102(24):8483-8.

Vallone B, Nienhaus K, Matthes A, Brunori M, Nienhaus GU. (2004)
The structure of carbonmonoxy neuroglobin reveals a heme-sliding mechanism for control of ligand affinity. Proc Natl Acad Sci U S A., 101(50):17351-6.

 Vallone B, Nienhaus K, Brunori M, Nienhaus GU. (2004)
The structure of murine neuroglobin: Novel pathways for ligand migration and binding. Proteins., 56(1):85-92.