PROSITE documentation PDOC51808
Coiled coil-helix-coiled coil-helix (CHCH) domain profile


Twin CX(9)C proteins constitute a large protein family among all eukaryotes. They adopt a coiled coil-helix-coiled coil helix (CHCH) fold stabilized by two disulfide bonds which are formed by the four cysteines in the twin CX(9)C motifs (i.e. two pairs of cysteines each spaced by nine residues). The large majority of twin CX(9)C proteins contains a single CHCH domain, while the others contain two. In those containing a single CHCH domain, this is most frequently located in the central part of the sequence, with C-terminal and N-terminal CHCH domains being less common. In those containing two CHCH domains, these are separated by a few amino acids and, taken together, typically cover a large central part of the sequence. A strong link exists between twin CX(9)C proteins and mitochondrial metabolism. Twin CX(9)C proteins are involved in a limited number of tasks, most if not all of which are performed in the mitochondrial inter-membrane space (IMS), and which include being part of protein complexes, participating in cytochrome c oxidase (COX) assembly, and maintaining mitochondrial structure. The functions of most twin CX(9)C proteins vary around the common theme of playing a scaffolding role which can tie their observed roles in mitochondrial structure and function [1,2,3].

The CHCH domain contains two α-helices (α1 and α2), which form an antiparallel α-hairpin that is covalently paired by two disulfide bridges (see <PDB:4YTV>) [4,5].

Some proteins known to contain a CHCH domain are listed below:

  • Cox17, a copper chaperone acting in cytochrome c oxydase biogenesis. It binds a copper(I) ion through an additional CC motif in the N-teminal region.
  • Cytochrome c oxidase subunit 6b-1 and 2 (COX6B-1 and 2), in which the four disulfide-bonded cysteines occur in a CX9C-CX10C rather than in a perfect twin CX(9)C motif.
  • Mia40, the central component of a system for protein import into the IMS. It promotes the oxidative folding of substrate proteins by a thiol- disulfide exchange mechanism and thus traps them in the IMS.
  • NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 (NDUFS5), accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
  • NADH dehydrogenase [ubiquinone] 1 α subcomplex subunit 8 (NDUFA8), accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
  • NADH dehydrogenase [ubiquinone] 1 β subcomplex subunit 7 (NDUFB7), accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
  • CX(9)C motif-containing protein 1 to 4 (CMC1 to CMC4).
  • Coiled coil-helix-coiled coil-helix domain-containing protein 1 (CHCHD1),
  • Mdm35, involved in mitochondrial distribution and morphology.

The profile we developed covers the entire CHCH domain.

Last update:

August 2016 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

CHCH, PS51808; Coiled coil-helix-coiled coil-helix (CHCH) domain profile  (MATRIX)


1AuthorsWesterman B.A. Poutsma A. Steegers E.A.P. Oudejans C.B.M.
TitleC2360, a nuclear protein expressed in human proliferative cytotrophoblasts, is a representative member of a novel protein family with a conserved coiled coil-helix-coiled coil-helix domain.
SourceGenomics 83:1094-1104(2004).
PubMed ID15177562

2AuthorsCavallaro G.
TitleGenome-wide analysis of eukaryotic twin CX9C proteins.
SourceMol. Biosyst. 6:2459-2470(2010).
PubMed ID20922212

3AuthorsLongen S. Bien M. Bihlmaier K. Kloeppel C. Kauff F. Hammermeister M. Westermann B. Herrmann J.M. Riemer J.
TitleSystematic analysis of the twin cx(9)c protein family.
SourceJ. Mol. Biol. 393:356-368(2009).
PubMed ID19703468

4AuthorsBanci L. Bertini I. Ciofi-Baffoni S. Jaiswal D. Neri S. Peruzzini R. Winkelmann J.
TitleStructural characterization of CHCHD5 and CHCHD7: two atypical human twin CX9C proteins.
SourceJ. Struct. Biol. 180:190-200(2012).
PubMed ID22842048

5AuthorsWatanabe Y. Tamura Y. Kawano S. Endo T.
TitleStructural and mechanistic insights into phospholipid transfer by Ups1-Mdm35 in mitochondria.
SourceNat. Commun. 6:7922-7922(2015).
PubMed ID26235513

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