PS51371

CBS domain profile

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Member databasePROSITE profiles
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Short nameCBS

Description

CBS domains contain about 60 amino acid residues and occur as tandem pairs in a variety of proteins in bacteria, archaea, and eukaryotes
[4]
[6]
. They are mainly found in proteins that are regulated by adenosyl metabolites. Depending on the protein in which they occur, CBS domains have been proposed to affect multimerization and sorting of proteins, channel gating, and ligand binding. However, recent experiments revealing that CBS domains can bind adenosine-containing ligands such ATP, AMP, or S-adenosylmethionine have led to the hypothesis that CBS domains function as sensors of intracellular metabolites
[1]
[3]
. Crystallographic studies of CBS domains have shown that pairs of CBS sequences form a globular domain where each CBS unit adopts a beta-alpha-beta-beta-alpha pattern
[5]
. Crystal structure of the CBS domains of the AMP-activated protein kinase in complexes with AMP and ATP shows that the phosphate groups of AMP/ATP lie in a surface pocket at the interface of two CBS domains, which is lined with basic residues, many of which are associated with disease-causing mutations
[2]
. Some proteins known to contain a CBS domain: - Cystathione beta-synthase (CBS) protein. CBS performs a crucial step in the biosynthetic pathway of cysteine by providing a regulatory control point for S-adenosylmethionine. - Mammalian AMP-activated protein kinase (AMPK) gamma-subunit. AMPK is a heterotrimer of three different subunits (alpha, beta, and gamma) with alpha being the catalytic subunit and beta and gamma having regulatory roles. AMPK is a serine/threonine protein kinase that has a central role in controlling whole-body metabolism in response to nutrients and hormonal signals. - Inosine-5'-monophosphate dehydrogenase (IMPDH) protein. This enzyme catalyzes the first committed step in the purine nucleoside-synthesis pathway for the generation of GMP. - CLC Chloride Channel family. These channels are voltage gated chloride channels that sustain a wide variety of cellular functions, including membrane excitability, synaptic communication, transepithelial transport, cell volume regulation, cell proliferation, and acidification of endosomes and lysosomes. - Glycine betaine/carnitine/choline transport ATP-binding protein. an ABC transporter involved in a high affinity multicomponent binding-protein-dependent transport system for glycine betaine, carnitine and choline; probably responsible for energy coupling to the transport system. The profile we developed covers the entire CBS domain.

References

1.CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. Scott JW, Hawley SA, Green KA, Anis M, Stewart G, Scullion GA, Norman DG, Hardie DG. J. Clin. Invest. 113, 274-84, (2004). View articlePMID: 14722619

2.Structural basis for AMP binding to mammalian AMP-activated protein kinase. Xiao B, Heath R, Saiu P, Leiper FC, Leone P, Jing C, Walker PA, Haire L, Eccleston JF, Davis CT, Martin SR, Carling D, Gamblin SJ. Nature 449, 496-500, (2007). View articlePMID: 17851531

3.Bateman domains and adenosine derivatives form a binding contract. Kemp BE. J. Clin. Invest. 113, 182-4, (2004). View articlePMID: 14722609

4.The structure of a domain common to archaebacteria and the homocystinuria disease protein. Bateman A. Trends Biochem. Sci. 22, 12-3, (1997). View articlePMID: 9020585

5.Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase. Zhang R, Evans G, Rotella FJ, Westbrook EM, Beno D, Huberman E, Joachimiak A, Collart FR. Biochemistry 38, 4691-700, (1999). View articlePMID: 10200156

6.CBS domains: structure, function, and pathology in human proteins. Ignoul S, Eggermont J. Am. J. Physiol., Cell Physiol. 289, C1369-78, (2005). View articlePMID: 16275737

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