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Function
Chaperone protein ClpB (ClpB) or Caseinolytic peptidase B protein homolog or suppressor of potassium transport defect 3 reactivates aggregated proteins in cooperation with Hsp70[1]. ClpB is an ATP-dependent chaperone which can rescue proteins from an aggregated state.
Disease
ClpB deficiency is a rare disorder characterized by neurological problems and shortage of white blood cells[2]. ClpB mutations cause progressive brain atrophy[3].
Structural highlights
The 3D structure of ClpB trimeric complex with the nucleotide AMPPNP shows the chaperone to be comprised of several domains: N-terminal, first nucleotide-binding domain (NBD1), a long coiled-coil linker domain, a second NBD and a D2 small domain. The first nucleotide AMPPNP binding site at NBD1 includes several hydrophobic residues as does the second NBD[4]. The long coiled-coil segments are implicated in the desaggregase activity of ClpB via their ability to move in opposite directions between subunits generating the mechanical force needed.
ClpB 3D structures
3D structures of ClpB
- ↑ Carroni M, Kummer E, Oguchi Y, Wendler P, Clare DK, Sinning I, Kopp J, Mogk A, Bukau B, Saibil HR. Head-to-tail interactions of the coiled-coil domains regulate ClpB activity and cooperation with Hsp70 in protein disaggregation. Elife. 2014 Apr 30;3:e02481. doi: 10.7554/eLife.02481. PMID:24843029
- ↑ Wortmann SB, Wevers RA. CLPB Deficiency PMID:27891836
- ↑ Wortmann SB, Zietkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC, Rakovic A, Renkema GH, Rodenburg RJ, Strom TM, Meitinger T, Rubio-Gozalbo ME, Chrusciel E, Distelmaier F, Golzio C, Jansen JH, van Karnebeek C, Lillquist Y, Lucke T, Ounap K, Zordania R, Yaplito-Lee J, van Bokhoven H, Spelbrink JN, Vaz FM, Pras-Raves M, Ploski R, Pronicka E, Klein C, Willemsen MA, de Brouwer AP, Prokisch H, Katsanis N, Wevers RA. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet. 2015 Feb 5;96(2):245-57. doi: 10.1016/j.ajhg.2014.12.013. Epub, 2015 Jan 15. PMID:25597510 doi:https://dx.doi.org/10.1016/j.ajhg.2014.12.013
- ↑ Lee S, Sowa ME, Watanabe YH, Sigler PB, Chiu W, Yoshida M, Tsai FT. The structure of ClpB: a molecular chaperone that rescues proteins from an aggregated state. Cell. 2003 Oct 17;115(2):229-40. PMID:14567920
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