Sandbox Reserved 335: Difference between revisions
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{{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}} | {{STRUCTURE_3cp5 | PDB=3cp5 | SCENE=Sandbox_Reserved_335/Cyt_c/2}} | ||
The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution. | The '''cytochrome ''c''''' (cyt ''c'') proteins are a superfamily belonging to the class of [http://en.wikipedia.org/wiki/All-α_proteins all-α proteins], which are denoted as such by having an α-helical core. Each protein in this superfamily also contains one or more covalently-bound [http://en.wikipedia.org/wiki/Heme heme prosthetic groups].<ref>PMID:11697912</ref><ref name=main /> The cyt ''c'' superfamily contains many different families, some of which are better characterized than others. These families include monodomain and multi-domain C-type cytochromes, such as [http://proteopedia.org/wiki/index.php/1etp cyt c4], a diheme C-type cytochrome, and [http://proteopedia.org/wiki/index.php/2ozy NrfB], a pentaheme C-type cytochrome. In particular, the monoheme cyt ''c'' from ''Rhodothermus marinus'' has been previously studied and provides an excellent example of how some protein characteristics and structures can be extremely diverse, yet conserved, through evolution. | ||
== Introduction == | == Introduction == | ||
[http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of | [http://en.wikipedia.org/wiki/Cytochrome Cytochromes] are a class of heme-containing proteins found in bacteria and the mitochondria of eukaryotes.<ref name=main /> These proteins are generally membrane-bound and are known as respiratory pigments because they are involved in various electron transport systems in oxidative phosphorylation.<ref name="heme">PMID:14871137</ref> Cytochromes can be categorized into several different types, three of which are based on the type of heme group the cytochrome contains: cytochromes ''a'', ''b'' and ''d'' contain heme ''a'', ''b'' and ''d'', respectively.<ref name=amb /> Cytochrome ''c'' is named such because it contains the heme ''c'', but is mainly distinguished from cytochromes ''a'', ''b'' and ''d'' due to the heme being coordinated with the protein scaffold by cysteinyl residues covalently bound to either one or both of the heme's vinyl side chains.<ref name=heme /> | ||
'' | Cyt ''c'' has been split into four classes.<ref name=amb>PMID:1646017</ref> Class I contains soluble, low spin<ref name=main /> single domain C-type cytochromes, of which there has been at least six subclasses found in prokaryotes including [http://en.wikipedia.org/wiki/Desulfovibrio ''Desulfovibrio desulfuricans''], [http://en.wikipedia.org/wiki/Rhodospirillum_rubrum ''Rhodospirillum rubrum''], and ''Rhodothermus marinus''. Cyt ''c'' in this class have a single heme attached close to the N-terminus of the polypeptide, with a methionine residue being the sixth iron coordination site. Class II contains higher spin-state cytochromes ''c'', such as cyt ''c''', with the heme being attached closer to the C-terminus. Class III contains cytochromes with multiple heme groups; these proteins have lower redox potentials compared to the other three classes<ref name=amb />. Finally, Class IV is comprised of more complex proteins with higher molecular weights containing heme ''c'' as well as other prosthetic groups.<ref name=class>Cookson DJ, Moore GR, Pitt RC, Williams RJP, Campbell ID, Ambler RP, Bruschi M, Le Gall J. Structural homology of cytochromes c. Eur J Biochem. 1978 Feb;83(1):261-75.</ref> | ||
== | == ''Rhodothermus marinus'' cytochrome ''c'' == | ||
=== Structure === | |||
<Structure load='3cp5' size='300' frame='true' align='right' caption='Figure 1. The heme group of monoheme cytochrome ''c'' purified from ''Rhodothermus marinus''.' scene='Sandbox_Reserved_335/Heme/1' /> | |||
All members in the C-type cytochrome superfamily contain a heme prosthetic group that is covalently attached to the protein via two thioether bonds to cysteine residues. Most cytochromes ''c'' occur in a <scene name='Sandbox_Reserved_335/Motif/1'>CXXCH motif</scene> where the histidine residue is one of the two axial ligands of the heme iron.<ref name=main>PMID:18855424</ref><ref name=heme /> In monoheme cytochromes ''c'', the other axial position may be left vacant or be occupied by histidine or methionine residues; however, it can sometimes be occupied by cysteine or lysine residues.<ref name=main />. In ''Rm''cyt''c'', XX represents a threonine (Thr46) and an alanine residue (Ala47) that help form the loop 2 structure. | |||
The heme prosthetic group | [[Image:heme.gif |frame|left| Figure 2. The tetrapyrrolic heme prosthetic group that can either be covalently attached to or closely associated with various proteins, such as cytochromes and other globin proteins. In ''Rm''cyt''c'', R2 is an ethyl group covalently attached to Cys 45, and R3 is a methyl group covalently attached to Cys48.]] | ||
The typical monoheme cyt ''c'' fold is formed by helices <scene name='Sandbox_Reserved_335/Helices/4'>A, C, and E</scene>. ''Rm''cyt''c'' contains seven α-helices that are folded around the heme, all connected by random coils.<ref name=main /> The heme group is axially coordinated by <scene name='Sandbox_Reserved_335/Axial/6'>His49 and Met100</scene>, and the disulfide linkages exist at <scene name='Sandbox_Reserved_335/Cys/1'>Cys45 and Cys48</scene>. The heme group in ''Rm''cyt''c'' is almost completely shielded from solvent due to it being in a mostly hydrophobic pocket. This pocket is formed in part by the seven helices surrounding the ring, but also by two structures that are uncommon in other cytochromes ''c''. First, a 21 amino acid extension of the N-terminal exists, forming <scene name='Sandbox_Reserved_335/Uncommon1/2'>α-helix A' and loop 1</scene>, which wraps around the back of the polypeptide.<ref name=main /> An extension resembling such has only been seen in ''Thermus thermophilus''; however, the extension occurs at the C-terminus rather than the N-terminus.<ref>doi:10.1006/jmbi.1997.1181</ref> A second rarity is that of <scene name='Sandbox_Reserved_335/Uncommon2/2'>helix B'</scene>, inserted between helix D and loop 3, that shields the bottom part of the heme from any solvent.<ref name=main /> In cytochrome ''c''<sub>2</sub> as well as mitochondrial cyt ''c'', a similar yet shorter helix was found, though this helix was present at a different place in the primary sequence. Also, instead of helix B', ''T. thermophilus'' contains a two-stranded [http://en.wikipedia.org/wiki/Beta_sheet β-sheet].<ref name=main /> One final note is the number of <scene name='Sandbox_Reserved_335/Met/1'>methionine</scene> residues that ''Rm''cyt''c'' contains. In general, cyt ''c'' contains about two methionines whereas ''Rm''cyt''c'' contains seven, located on the left of the heme.<ref name=main /> | |||
As determined by X-ray crystallography, the ''Rm''cyt''c'' structure was found to contain a sulfate ion coordinated to Glu122 via hydrogen bonding to the protonated carboxylate oxygen. In the protein complex, this ion has been seen to mediate crystal contact between neighbouring protein molecules.<ref name=main /> | |||
The observation of these structural motifs in other C-type cytochromes can support the divergent evolution of cytochromes ''c''.<ref name=main /> These motifs are present in a number of different bacteria and are seen in similar regions of the secondary structure; however, they exist in the primary sequence in places distinct to the phylum. For example, monoheme cytochromes ''c'' in the rest of the Bacteroidetes phylum have an N-terminus extension that is highly conserved to that of ''Rm''cyt''c'', and the regions in the primary structure that correspond to these secondary motifs are not observed in other bacterial phyla.<ref name=main /> Also, due to these motifs being absent from other phyla, the Bacteroidetes monoheme cyt ''c'' has been said to form a new subfamily of cyt ''c''. | |||
== Function == | == Function == | ||
Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''<sub>1</sub> complexes | Monoheme cytochromes ''c'' are involved in electron transport chains in both prokaryotes and eukaryotic mitochondria.<ref name=main /> They mediate the transfer of electrons mainly from the ''bc''<sub>1</sub> complexes or their analogs to heme-copper oxygen reductases (HCOs) in the [http://en.wikipedia.org/wiki/Electron_transport_chain electron transport chain] of [http://en.wikipedia.org/wiki/Oxidative_phosphorylation oxidative phosphorylation]. Heme ''c'' containing domains are often found fused to other protein domains such as these HCOs, including the ''caa''<sub>3</sub> oxygen reductases<ref name=main /><ref>PMID:14691678</ref>; these enzymes are membrane-bound and catalyze the reduction of O<sub>2</sub> to water.<ref>PMID:11334784</ref> In addition to being involved in oxidative phosphorylation, monoheme cyt ''c'' has also been seen to participate in the electron transport chain of [http://en.wikipedia.org/wiki/Photosynthesis photosynthesis].<ref name=main /> | ||
In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is | In addition to being involved in the electron transfer in many systems, cyt c is involved in cell apoptosis, the programmed death of a cell due to cellular signals. Cyt c is | ||
=== | === Electron transport chain === | ||
In the electron transport chain, cyt c shuttles electrons between the respiratory complexes III and IV. | In the electron transport chain (ETC), cyt ''c'' shuttles electrons between the respiratory complexes III and IV; complex III is the cytochrome ''bc''<sub>1</sub> complex and IV is cyt ''c'' oxidase. Initially, the heme iron in cyt ''c'' is in the reduced, Fe<sup>3+</sup> state; this allows for the uptake of one electron, oxidizing the iron to the Fe<sup>2+</sup> state.<ref name='etc'>ISBN:10-0-470-04217-6</ref> The ETC in eukaryotes is quite simple compared to that of prokaryotes. | ||
=== Apoptosis === | |||
== Importance == | == Importance == | ||
C-type cytochromes are required for the apoptotic and electron transfer processes to function properly.<ref name=apop>doi:10.1038/ng.103</ref> | |||
== References == | == References == | ||
<references/> | <references/> | ||
