Electron-transferring flavoprotein

Last updated
Electron transfer flavoprotein domain
PDB 1efp EBI.jpg
electron transfer flavoprotein (etf) from paracoccus denitrificans
Identifiers
SymbolETF
Pfam PF01012
Pfam clan CL0039
InterPro IPR014730
PROSITE PDOC00583
SCOP2 1efv / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Electron transfer flavoprotein FAD-binding domain
PDB 1o96 EBI.jpg
structure of electron transferring flavoprotein for methylophilus methylotrophus.
Identifiers
SymbolETF_alpha
Pfam PF00766
Pfam clan CL0085
InterPro IPR014731
PROSITE PDOC00583
SCOP2 1efv / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

An electron transfer flavoprotein (ETF) [1] or electron transfer flavoprotein complex (CETF) is a flavoprotein located on the matrix face of the inner mitochondrial membrane and functions as a specific electron acceptor for primary dehydrogenases, transferring the electrons to terminal respiratory systems such as electron-transferring-flavoprotein dehydrogenase. They can be functionally classified into constitutive, "housekeeping" ETFs, mainly involved in the oxidation of fatty acids (Group I), and ETFs produced by some prokaryotes under specific growth conditions, receiving electrons only from the oxidation of specific substrates (Group II). [2]

Contents

ETFs are heterodimeric proteins composed of an alpha and beta subunit (ETFA and ETFB), and contain an FAD cofactor and AMP. [3] [4] ETF consists of three domains: domains I and II are formed by the N- and C-terminal portions of the alpha subunit, respectively, while domain III is formed by the beta subunit. Domains I and III share an almost identical alpha-beta-alpha sandwich fold, while domain II forms an alpha-beta-alpha sandwich similar to that of bacterial flavodoxins. FAD is bound in a cleft between domains II and III, while domain III binds the AMP molecule. Interactions between domains I and III stabilise the protein, forming a shallow bowl where domain II resides.

LYRM5, a member of the LYRM protein superfamily, deflavinates ETF by interacting with both ETFA and ETFB. [5] This destabilizes the FAD-binding site, leading to the release of FAD and, subsequently, to the disruption of electron transfer. [5]

Mutation in ETFs can lead to deficiency of passing reducing equivalent of FADH2 to electron transport chain, causing Glutaric acidemia type 2

See also

References

  1. Logan CM, Rice MK (1987). Logan's Medical and Scientific Abbreviations (Hardbound book). J. B. Lippincott. p. 182. ISBN   0-397-54589-4.
  2. Weidenhaupt M, Rossi P, Beck C, Fischer HM, Hennecke H (1996). "Bradyrhizobium japonicum possesses two discrete sets of electron transfer flavoprotein genes: fixA, fixB and etfS, etfL". Arch. Microbiol. 165 (3): 169–78. Bibcode:1996ArMic.165..169W. doi:10.1007/BF01692858. PMID   8599534.
  3. Tsai MH, Saier MH (1995). "Phylogenetic characterization of the ubiquitous electron transfer flavoprotein families ETF-alpha and ETF-beta". Res. Microbiol. 146 (5): 397–404. doi: 10.1016/0923-2508(96)80285-3 . PMID   8525056.
  4. Roberts DL, Frerman FE, Kim JJ (1996). "Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14355–60. doi: 10.1073/pnas.93.25.14355 . PMC   26136 . PMID   8962055.
  5. 1 2 Floyd, Brendan J.; Wilkerson, Emily M.; Veling, Mike T.; Minogue, Catie E.; Xia, Chuanwu; Beebe, Emily T.; Wrobel, Russell L.; Cho, Holly; Kremer, Laura S.; Alston, Charlotte L.; Gromek, Katarzyna A.; Dolan, Brendan K.; Ulbrich, Arne; Stefely, Jonathan A.; Bohl, Sarah L. (August 2016). "Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function". Molecular Cell. 63 (4): 621–632. doi: 10.1016/j.molcel.2016.06.033 . ISSN   1097-2765. PMC   4992456 . PMID   27499296.