title: Neuroglobin and cytoglobin: Two new entries in the hemoglobin superfamily*.
abstract: Neuroglobin (Ngb) and cytoglobin (Cygb) are two newly discovered intracellular members of the vertebrate hemoglobin (Hb) family. Ngb, predominantly expressed in nerve cells, is of ancient evolutionary origin and is homologous to nerve-globins of invertebrates. Cygb, present in many different tissues, shares common ancestry with myoglobin (Mb) and can be traced to early vertebrate evolution. Ngb and Cygb display the classical three-on-three α-helical globin fold and are endowed with a hexa-coordinate heme Fe atom, in both their ferrous and ferric forms, having the heme distal HisE7 residue as the endogenous sixth ligand. Reversible intramolecular hexa- to penta-coordination of the heme Fe atom modulates Ngb and Cygb ligand-binding properties. In Ngb and Cygb, ligand migration to/from the heme distal site may be assisted by protein/matrix tunnel cavity systems. The physiological roles of Ngb and Cygb are poorly understood. Ngb may protect neuronal cells from hypoxic-ischemic insults, may act as oxidative stress-responsive sensor protein, and may sustain NO/O(2) scavenging and/or reactive oxygen species (ROS) detoxification. Cygb, located in the cytoplasm of fibroblasts, chondroblasts, osteoblasts, and hepatic stellate cells, has been hypothesized to be involved in collagen synthesis. In neurons, Cygb, located in both cytoplasm and nucleus, may provide O(2) for enzymatic reactions, and may be involved in a ROS (NO)-signaling pathway(s). Here, we review current knowledge on Ngb and Cygb in terms of their structure, function, and evolutionary links to the well-known human HbA and Mb.
authors.affiliation: Department of Biology and the Interdepartmental Laboratory for Electron Microscopy, University "Roma Tre," I-00146 Roma, Italy; National Institute for Infectious Diseases IRCSS "Lazzaro Spallanzani," I-00149 Roma, Italy. ascenzi@bio.uniroma3.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Alessio
authors.initials: A
authors.lastname: Bocedi
authors.forename: Daniele
authors.initials: D
authors.lastname: de Sanctis
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pesce
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.forename: Michael C
authors.initials: MC
authors.lastname: Marden
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.forename: Luc
authors.initials: L
authors.lastname: Moens
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankeln
authors.forename: Thorsten
authors.initials: T
authors.lastname: Burmester