Limits...
The novel component Kgd4 recruits the E3 subunit to the mitochondrial α-ketoglutarate dehydrogenase.

Heublein M, Burguillos MA, Vögtle FN, Teixeira PF, Imhof A, Meisinger C, Ott M - Mol. Biol. Cell (2014)

Bottom Line: Biochemical analyses demonstrate that this protein plays an evolutionarily conserved role in the organization of mitochondrial α-KGDH complexes of fungi and animals.By binding to both the E1-E2 core and the E3 subunit, Kgd4 acts as a molecular adaptor that is necessary to a form a stable α-KGDH enzyme complex.Our work thus reveals a novel subunit of a key citric acid-cycle enzyme and shows how this large complex is organized.

View Article: PubMed Central - PubMed

Affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.

Show MeSH

Related in: MedlinePlus

Model for the organization of KGDH and the role of Kgd4. (A) Model. The novel subunit Kgd4 recruits the E3 subunit to the core of KGDH, formed by E1 and E2 subunits. The C-terminus of Kgd4 contacts Kgd1-Kgd2 core, while the N-terminus interacts with Lpd1. (B) In the absence of Kgd4, the contact of E3 to the core is dramatically reduced.
© Copyright Policy - creative-commons
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4214781&req=5

Figure 8: Model for the organization of KGDH and the role of Kgd4. (A) Model. The novel subunit Kgd4 recruits the E3 subunit to the core of KGDH, formed by E1 and E2 subunits. The C-terminus of Kgd4 contacts Kgd1-Kgd2 core, while the N-terminus interacts with Lpd1. (B) In the absence of Kgd4, the contact of E3 to the core is dramatically reduced.

Mentions: To test this, we purified complexes of Kgd4ΔN and found that Kgd1 and Kgd2 but not Lpd1 could be copurified with this protein (Figure 7C). This demonstrates that the C-terminal domain of Kgd4 directly interacts with the assembled Kgd1-Kgd2 core because a direct interaction of Kgd4 with Kgd2 can be ruled out according to previous experiments (Figure 5A). Taken together, these data establish that Kgd4 contains two functionally separable domains. While the C-terminal domain is required to establish interactions with the Kgd1-Kgd2 core, the N-terminal domain binds to the E3 subunit Lpd1 (Figure 8A). This architecture likely enables Kgd4 to act as a molecular adaptor between the E3 subunit and the core of KGDH.


The novel component Kgd4 recruits the E3 subunit to the mitochondrial α-ketoglutarate dehydrogenase.

Heublein M, Burguillos MA, Vögtle FN, Teixeira PF, Imhof A, Meisinger C, Ott M - Mol. Biol. Cell (2014)

Model for the organization of KGDH and the role of Kgd4. (A) Model. The novel subunit Kgd4 recruits the E3 subunit to the core of KGDH, formed by E1 and E2 subunits. The C-terminus of Kgd4 contacts Kgd1-Kgd2 core, while the N-terminus interacts with Lpd1. (B) In the absence of Kgd4, the contact of E3 to the core is dramatically reduced.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214781&req=5

Figure 8: Model for the organization of KGDH and the role of Kgd4. (A) Model. The novel subunit Kgd4 recruits the E3 subunit to the core of KGDH, formed by E1 and E2 subunits. The C-terminus of Kgd4 contacts Kgd1-Kgd2 core, while the N-terminus interacts with Lpd1. (B) In the absence of Kgd4, the contact of E3 to the core is dramatically reduced.
Mentions: To test this, we purified complexes of Kgd4ΔN and found that Kgd1 and Kgd2 but not Lpd1 could be copurified with this protein (Figure 7C). This demonstrates that the C-terminal domain of Kgd4 directly interacts with the assembled Kgd1-Kgd2 core because a direct interaction of Kgd4 with Kgd2 can be ruled out according to previous experiments (Figure 5A). Taken together, these data establish that Kgd4 contains two functionally separable domains. While the C-terminal domain is required to establish interactions with the Kgd1-Kgd2 core, the N-terminal domain binds to the E3 subunit Lpd1 (Figure 8A). This architecture likely enables Kgd4 to act as a molecular adaptor between the E3 subunit and the core of KGDH.

Bottom Line: Biochemical analyses demonstrate that this protein plays an evolutionarily conserved role in the organization of mitochondrial α-KGDH complexes of fungi and animals.By binding to both the E1-E2 core and the E3 subunit, Kgd4 acts as a molecular adaptor that is necessary to a form a stable α-KGDH enzyme complex.Our work thus reveals a novel subunit of a key citric acid-cycle enzyme and shows how this large complex is organized.

View Article: PubMed Central - PubMed

Affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.

Show MeSH
Related in: MedlinePlus