Abstract
The nerve tissue mini-hemoglobin from Cerebratulus lacteus (CerHb) displays an essential globin fold hosting a protein matrix tunnel held to allow traffic of small ligands to and from the heme. CerHb heme pocket hosts the distal TyrB10/GlnE7 pair, normally linked to low rates of O2 dissociation and ultra-high O2 affinity. However, CerHb affinity for O2 is similar to that of mammalian myoglobins, due to a dynamic equilibrium between high and low affinity states driven by the ability of ThrE11 to orient the TyrB10 OH group relative to the heme ligand. We present here the high resolution crystal structures of CerHb in the unligated and carbomonoxy states. Although CO binds to the heme with an orientation different from the O2 ligand, the overall binding schemes for CO and O2 are essentially the same, both ligands being stabilized through a network of hydrogen bonds based on TyrB10, GlnE7, and ThrE11. No dramatic protein structural changes are needed to support binding of the ligands, which can freely reach the heme distal site through the apolar tunnel. A lack of main conformational changes between the heme-unligated and -ligated states grants stability to the folded mini-Hb and is a prerequisite for fast ligand diffusion to/from the heme.
Highlights
The nerve haemoglobin (Hb) from the nemertean worm Cerebratulus lacteus (CerHb) is one of the smallest naturally occurring known globins, being composed of 109 amino acids instead of the~140–160 residues typical of most globins [1,2]
The heme Fe atom is regularly coordinated to the proximal His(93)F8 residue, while on the distal site O2 stabilization is achieved through a network of hydrogen bonds based on the three key residues: Tyr(11)B10, Gln(44)E7, and Thr(48)E11
Thr(48)E11 participates in this process by fine tuning the Tyr(11)B10 OH group orientation relative to the O2 ligand molecule
Summary
The nerve haemoglobin (Hb) from the nemertean worm Cerebratulus lacteus (CerHb) is one of the smallest naturally occurring known globins, being composed of 109 amino acids instead of the. The heme Fe atom is regularly coordinated to the proximal His(93)F8 residue (amino acids have been identified with their topological site numbers as defined in the conventional globin fold), while on the (ligand binding) distal site O2 stabilization is achieved through a network of hydrogen bonds based on the three key residues: Tyr(11)B10, Gln(44)E7, and Thr(48)E11. A second distinct structural feature of CerHb is the presence of a long apolar tunnel that traverses the interior of the globin matrix from the heme pocket to the solvent, between the C-terminal ends of the E and H helices [3] This tunnel allows a relatively unhindered access to the distal portion of the heme pocket and correlates with an unusually large association rate constant for O2 binding to CerHb (k’O2 = 240 μM−1·s−1), when compared with those of other invertebrate globins containing the Tyr-Gln active site motif (1 to 5 μM−1·s−1) [6]. We show that the overall protein structure in the distal site and in the apolar tunnel is unperturbed by ligand binding; the CO and O2 ligands bind the heme Fe-atom with different orientations, while exploiting very similar H-bonding stabilization schemes within the distal site
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