B561

Cytochrome b-561 / ferric reductase transmembrane domain.

• SMART accession number: SM00665
• Description: Cytochrome b-561 recycles ascorbate for the generation of norepinephrine by dopamine-beta-hydroxylase in the chromaffin vesicles of the adrenal gland. It is a transmembrane heme protein with the two heme groups being bound to conserved histidine residues. A cytochrome b-561 homologue, termed Dcytb, is an iron-regulated ferric reductase in the duodenal mucosa. Other homologues of these are also likely to be ferric reductases. SDR2 is proposed to be important in regulating the metabolism of iron in the onset of neurodegenerative disorders.
• Interpro abstract (IPR006593):

  Cytochromes b561 constitute a class of intrinsic membrane proteins containing two haem molecules that are involved in ascorbate (vitamin C) regeneration. They have been suggested to function as electron transporters, shuttling electrons across membranes from ascorbate to an acceptor molecule. The one-electron oxidation product of ascorbate, monodehydro-ascorbate (MDHA) has been shown to function as an electon acceptor for mammalian and plant cytochromes b561. The cytochrome b561-catalysed reduction of MDHA results in the regeneration of the fully reduced ascorbate molecule. Cytochromes b561 have been identified in a large number of phylogenetically distant species, but are absent in prokaryotes. Most species contain three or four cytochrome b561 paralogous proteins [ (PUBMED:12801412) ].

  Members of the cytochrome b561 protein family are characterised by a number of structural features, likely to play an essential part in their function. They are highly hydrophobic proteins with six transmembrane helices (named TMH1 through TMH6), four conserved histidine residues, probably coordinating the two haem molecules, and predicted substrate-binding sites for ascorbate and MDHA [ (PUBMED:12801412) ]. The functionally relevant and structurally most conserved region in the cytochrome b561 family is the TMH2 to -5 4-helix core with an amino acid composition that is very well conserved in the inner surface and somewhat less conserved in the outer surface of the core. The two terminal helices (TMH1 and TMH6) are less conserved [ (PUBMED:11532994) (PUBMED:12768339) ].

  The entry represents a conserved region containing six transmembrane helices, found in cytochrome b651 and homologous proteins including some ferric reductases.

There are 4061 B561 domains in 4037 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Binding / catalysis: Binds heme. Reduces Fe(III) to Fe(II).

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• McKie AT et al.
• An iron-regulated ferric reductase associated with the absorption ofdietary iron.
• Science. 2001; 291: 1755-9

The ability of intestinal mucosa to absorb dietary ferric iron isattributed to the presence of a brush-border membrane reductase activitythat displays adaptive responses to iron status. We have isolated acomplementary DNA, Dcytb (for duodenal cytochrome b), which encoded aputative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytbshared between 45 and 50% similarity to the cytochrome b561 family ofplasma membrane reductases, was highly expressed in the brush-bordermembrane of duodenal enterocytes, and induced ferric reductase activitywhen expressed in Xenopus oocytes and cultured cells. Duodenal expressionlevels of Dcytb messenger RNA and protein were regulated by changes inphysiological modulators of iron absorption. Thus, Dcytb provides animportant element in the iron absorption pathway.

• Njus D, Kelley PM
• The secretory-vesicle ascorbate-regenerating system: a chain of concertedH+/e(-)-transfer reactions.
• Biochim Biophys Acta. 1993; 1144: 235-48

• DegliEsposti M, KamenskyYu A, Arutjunjan AM, Konstantinov AA
• A model for the molecular organization of cytochrome beta-561 inchromaffin granule membranes.
• FEBS Lett. 1989; 254: 74-8

The CD spectrum of reduced cytochrome (cyt.) beta-561 in chromaffingranule membranes resembles that of mitochondrial cyt. beta 1 andindicates possible heme-heme interaction in the protein. Based onspectroscopic data and analysis of the amino acid sequence, a model ofcyt. beta-561 is suggested, in which the protein carries twotransmembrane-localized hemes, each coordinated by two histidines. Themodel accounts for the presence of two different forms of cyt. beta-561 inchromaffin granule membranes and provides a mechanism of transmembraneelectron transfer by this hemoprotein.

Structure (3D structures containing this domain)

3D Structures of B561 domains in PDB

PDB code	Title
4o6y	Crystal Structure of Cytochrome b561
4o79	Crystal Structure of Ascorbate-bound Cytochrome b561, crystal soaked in 1 M L-ascorbate for 10 minutes
4o7g	Crystal Structure of Ascorbate-bound Cytochrome b561, crystal soaked in 1 M L-ascorbate for 40 minutes

Links (links to other resources describing this domain)

• INTERPRO: IPR006593