The globins are a superfamily of heme-containing , involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight Alpha helix. Two prominent members include myoglobin and hemoglobin. Both of these proteins reversibly bind oxygen via a heme prosthetic group. They are widely distributed in many .
Structure
Globin superfamily members share a common three-dimensional fold.
This 'globin fold' typically consists of eight
Alpha helix, although some proteins have additional helix extensions at their termini.
Since the globin fold contains only helices, it is classified as an all-alpha protein fold.
The globin fold is found in its namesake globin Protein families as well as in . The globin fold was thus the first protein fold discovered (myoglobin was the first protein whose structure was solved).
Helix packaging
The eight helices of the globin fold core share significant nonlocal structure, unlike other
in which
close to each other in
primary sequence are also close in space. The helices pack together at an average angle of about 50 degrees, significantly steeper than other helical packings such as the
helix bundle. The exact angle of helix packing depends on the sequence of the protein, because packing is mediated by the
and
hydrophobic interactions of the amino acid
near the helix interfaces.
Evolution
Globins
evolution from a common ancestor and can be divided into three lineages:
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Family M (for myoglobin-like) or F (for FHb-like),
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Subfamily FHb, for flavohemoglobins. Fusion protein.
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Subfamily SDgb, for single-domain globins (not to be confused with SSDgb).
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Family S (for sensor-like), again with a 3/3 fold.
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Subfamily GCS, for Globin-coupled sensors. Chimeric.
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Subfamily PGb, for protoglobins. Single-domain.
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Subfamily SSDgb, for sensor single-domain globins.
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Family T (for truncated), with a 2/2 fold
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Subfamily TrHb1 (also T1 or N).
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Subfamily TrHb2 (also T2 or O). Includes 2/2 .
-
Subfamily TrHb3 (also T3 or P).
The M/F family of globins is absent in archaea. Eukaryotes lack GCS, Pgb, and T3 subfamily globins.
Eight globins are known to occur in vertebrates: androglobin (Adgb), cytoglobin (Cygb), globin E (GbE, from bird eye), globin X (GbX, not found in mammals or birds), globin Y (GbY, from some mammals), hemoglobin (Hb), myoglobin (Mb) and neuroglobin (Ngb).[Solène Song, Viktor Starunov, Xavier Bailly, Christine Ruta, Pierre Kerner, Annemiek J. M. Cornelissen, Guillaume Balavoine: Globins in the marine annelid Platynereis dumerilii shed new light on hemoglobin evolution in bilaterians. In: BMC Evolutionary Biology Vol. 20, Issue 165. 29 December 2020. . See also:
] Several functionally different hemoglobins can coexist in the same species.
Sequence conservation
Although the fold of the globin superfamily is highly
conserved, the sequences that form the fold can have as low as 16% sequence identity. While the sequence specificity of the fold is not stringent, the
hydrophobic core of the protein must be maintained and hydrophobic patches on the generally
hydrophilic solvent-exposed surface must be avoided in order for the structure to remain stable and
soluble. The most famous mutation in the globin fold is a change from
glutamate to
valine in one chain of the hemoglobin molecule. This mutation creates a "hydrophobic patch" on the protein surface that promotes intermolecular aggregation, the molecular event that gives rise to sickle-cell disease.
Subfamilies
Examples
Human genes encoding globin proteins include:
-
Cytoglobin
-
HBA1, HBA2, HBB, HBD, HBE1, HBG1, HBG2, mu hemoglobin, HBQ1, HBZ, myoglobin
The globins include:
-
Haemoglobin (Hb)
-
Myoglobin (Mb)
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Neuroglobin: a myoglobin-like hemeprotein gene expression in vertebrate brain and retina, where it is involved in neuroprotection from damage due to hypoxia or ischemia.
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Cytoglobin: an oxygen sensor Gene expression in multiple tissues. Related to neuroglobin.
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Erythrocruorin: highly cooperative extracellular respiratory proteins found in and that are assembled from as many as 180 subunit into hexagonal bilayers.
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Leghaemoglobin (legHb or symbiosis Hb): occurs in the of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation.
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Non-symbiotic hemoglobin (NsHb): occurs in non-leguminous plants, and can be over-expressed in stressed plants .
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Flavohemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection against nitric oxide via its C-terminal domain, which transfers to heme in the globin.
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Globin E: a globin responsible for storing and delivering oxygen to the retina in birds
-
Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles the cell signalling domain of chemoreceptors. They bind oxygen, and act to initiate an aerotactic response or regulate gene expression.
-
Protoglobin: a single domain globin found in archaea that is related to the N-terminal domain of globin-coupled sensors.
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Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3 alpha helix sandwich protein folding. Can be divided into three main groups (I, II and II) based on structural features.
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HbN (or GlbN): a truncated hemoglobin-like protein that binds oxygen cooperatively with a very high affinity and a slow dissociation rate, which may exclude it from oxygen transport. It appears to be involved in bacterial nitric oxide detoxification and in nitrosative stress.
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Cyanoglobin (or GlbN): a truncated hemoprotein found in cyanobacteria that has high oxygen affinity, and which appears to serve as part of a terminal oxidase, rather than as a respiratory pigment.
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HbO (or GlbO): a truncated hemoglobin-like protein with a lower oxygen affinity than HbN. HbO associates with the bacterial cell membrane, where it significantly increases oxygen uptake over Cell membrane lacking this protein. HbO appears to interact with a terminal oxidase, and could participate in an oxygen/electron-transfer process that facilitates oxygen transfer during aerobic metabolism.
-
Glb3: a nuclear-encoded truncated hemoglobin from that appears more closely related to HbO than HbN. Glb3 from Arabidopsis thaliana (Mouse-ear cress) exhibits an unusual concentration-independent binding of oxygen and carbon dioxide.
The globin fold
The globin fold (cd01067) also includes some non-hem proteins. Some of them are the
, the N-terminal domain of two-component regulatory system
histidine kinase,
RsbR, and
RsbN.
See also
