Globin superfamily members share a commonthree-dimensional fold.[3] This 'globin fold' typically consists of eightalpha helices, although some proteins have additional helix extensions at their termini.[4] Since the globin fold contains only helices, it is classified as anall-alpha protein fold.
The globin fold is found in its namesake globinfamilies as well as inphycocyanins. The globin fold was thus the first protein fold discovered (myoglobin was the first protein whose structure was solved).
The eight helices of the globin fold core share significant nonlocal structure, unlike otherstructural motifs in whichamino acids close to each other inprimary 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 thehelix bundle. The exact angle of helix packing depends on the sequence of the protein, because packing is mediated by thesterics andhydrophobic interactions of the amino acidside chains near the helix interfaces.
Subfamily SSDgb, for sensor single-domain globins.
Family T (for truncated), with a 2/2 fold[8] All subfamilies can be chimeric, single-domain, or tandemly linked.[7]
Subfamily TrHb1 (also T1 or N).
Subfamily TrHb2 (also T2 or O). Includes 2/2phytoglobins.
Subfamily TrHb3 (also T3 or P).
The M/F family of globins is absent inarchaea. Eukaryotes lack GCS, Pgb, and T3 subfamily globins.[7]
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) andneuroglobin (Ngb).[7] All these types evolved from a single globin gene of F/M family[7] found in basal animals.[9] The single gene has also invented an oxygen-carrying "hemoglobin" multiple times in other groups of animals.[10] Several functionally different haemoglobins can coexist in the samespecies.
Although the fold of the globin superfamily is highlyevolutionarilyconserved, the sequences that form the fold can have as low as 16% sequence identity. While the sequence specificity of the fold is not stringent, thehydrophobic core of the protein must be maintained and hydrophobic patches on the generallyhydrophilic solvent-exposed surface must be avoided in order for the structure to remain stable andsoluble. The most famous mutation in the globin fold is a change fromglutamate tovaline 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 tosickle-cell disease.[citation needed]
Neuroglobin: a myoglobin-like haemproteinexpressed in vertebratebrain and retina, where it is involved in neuroprotection from damage due tohypoxia orischemia.[11] Neuroglobin belongs to a branch of the globin family that diverged early inevolution.
Flavohaemoglobins (FHb): chimeric, with an N-terminal globin domain and a C-terminalferredoxin reductase-like NAD/FAD-binding domain. FHb provides protection againstnitric oxide via its C-terminal domain, which transferselectrons to haem in the globin.[14]
Globin E: a globin responsible for storing and delivering oxygen to the retina in birds[15]
Globin-coupled sensors: chimeric, with an N-terminal myoglobin-like domain and a C-terminal domain that resembles thecytoplasmicsignalling domain ofbacterial chemoreceptors. Theybind oxygen, and act to initiate an aerotactic response orregulategene expression.[16][17]
Protoglobin: a single domain globin found inarchaea that is related to the N-terminal domain of globin-coupled sensors.[18]
Truncated 2/2 globin: lack the first helix, giving them a 2-over-2 instead of the canonical 3-over-3alpha-helical sandwichfold. Can be divided into three main groups (I, II and II) based onstructural features.
HbN (or GlbN): a truncated haemoglobin-like protein that binds oxygen cooperatively with a very high affinity and a slowdissociation rate, which may exclude it from oxygen transport. It appears to be involved inbacterial nitric oxidedetoxification and in nitrosativestress.[19]
Cyanoglobin (or GlbN): a truncated haemoprotein found incyanobacteria that has high oxygen affinity, and which appears to serve as part of a terminal oxidase, rather than as a respiratory pigment.[20]
HbO (or GlbO): a truncated haemoglobin-like protein with a lower oxygen affinity than HbN. HbO associates with the bacterialcell membrane, where itsignificantly increases oxygen uptake overmembranes lacking this protein. HbO appears tointeract with a terminal oxidase, and could participate in an oxygen/electron-transfer process that facilitates oxygen transfer duringaerobic metabolism.[21]
Glb3: a nuclear-encoded truncated haemoglobin fromplants that appears more closely related to HbO than HbN. Glb3 fromArabidopsis thaliana (Mouse-ear cress) exhibits an unusual concentration-independent binding of oxygen andcarbon dioxide.[22]
^Kavanaugh JS, Rogers PH, Case DA, Arnone A (April 1992). "High-resolution X-ray study of deoxyhemoglobin Rothschild 37 beta Trp----Arg: a mutation that creates an intersubunit chloride-binding site".Biochemistry.31 (16):4111–21.doi:10.1021/bi00131a030.PMID1567857.
^Vinogradov SN, Hoogewijs D, Bailly X, Mizuguchi K, Dewilde S, Moens L, Vanfleteren JR (August 2007). "A model of globin evolution".Gene.398 (1–2):132–42.doi:10.1016/j.gene.2007.02.041.PMID17540514.
^Branden, Carl; Tooze, John (1999).Introduction to protein structure (2nd ed.). New York: Garland Pub.ISBN978-0815323051.
^Bolognesi, M; Onesti, S; Gatti, G; Coda, A; Ascenzi, P; Brunori, M (1989). "Aplysia limacina myoglobin. Crystallographic analysis at 1.6 a resolution".Journal of Molecular Biology.205 (3):529–44.doi:10.1016/0022-2836(89)90224-6.PMID2926816.
^Freitas TA, Saito JA, Hou S, Alam M (January 2005). "Globin-coupled sensors, protoglobins, and the last universal common ancestor".J. Inorg. Biochem.99 (1):23–33.doi:10.1016/j.jinorgbio.2004.10.024.PMID15598488.
^Yeh DC, Thorsteinsson MV, Bevan DR, Potts M, La Mar GN (February 2000). "Solution 1H NMR study of the heme cavity and folding topology of the abbreviated chain 118-residue globin from the cyanobacterium Nostoc commune".Biochemistry.39 (6):1389–99.doi:10.1021/bi992081l.PMID10684619.
