Biology Reference
In-Depth Information
CHAPTER THREE
Protoglobin: Structure and
Ligand-Binding Properties
Alessandra Pesce
*
, Martino Bolognesi
†
,
{
, Marco Nardini
†
,1
*
Department of Physics, University of Genova, Genova, Italy
†
Department of Biosciences, University of Milano, Milano, Italy
{
CIMAINA and CNR Institute of Biophysics, Milano, Italy
1
Corresponding author: e-mail address: marco.nardini@unimi.it
Contents
1.
Introduction
80
2. Overall Structure
82
3. The Two-Tunnel System
85
4. The Haem Environment
87
5. Biochemical and Functional Characterisation
90
6. Conclusions
93
References
94
Abstract
Protoglobin is the first globin identified in Archaea; its biological role is still unknown,
although it can bind O
2
, CO and NO reversibly
. The X-ray structure of
Methanosarcina acetivorans protoglobin revealed several peculiar structural features.
Its tertiary structure can be considered as an expanded version of the canonical globin
fold, characterised by the presence of a pre-A helix (named Z) and a 20-residue
N-terminal extension. Other unusual trends are a large distortion of the haem moiety,
and its complete burial in the protein matrix due to the extended CE and FG loops and
the 20-residue N-terminal loop. Access of diatomic ligands to the haem has been pro-
posed to be granted by two tunnels, which are mainly defined by helices B/G (tunnel 1)
and B/E (tunnel 2), and whose spatial orientation and topology give rise to an almost
orthogonal two-tunnel system unprecedented in other globins. At a quaternary level,
protoglobin forms a tight dimer, mostly based on the inter-molecular four-helix bundle
built by the G- and H-helices, similar to that found in globin-coupled sensor proteins,
which share with protoglobin a common phylogenetic origin. Such unique structural
properties, together with an unusually low O
2
dissociation rate and a selectivity ratio
for O
2
/CO binding that favours O
2
ligation, make protoglobin a peculiar case for gaining
insight into structure to function relationships within the globin superfamily. While
recent structural and biochemical data have given answers to important questions,
the functional issue is still unclear and it is expected to represent the major focus of
future investigations.
in vitro
