Process_ProteinFolding – Protein folding

WID Process_ProteinFolding
Name Protein folding
Initialization order 5 View in model
Comments For some proteins, protein folding requires prosthetic groups including inorganic ions and/or molecular chaperones. See Note_Cofactors and Note_ProteinChaperones for information about the reconstruction of the specific prosthetic groups and chaperones required for the correct folding of each polypeptide. This module simulates: Prosthetic group complexation Inorganic ions: Fe2+, Fe3+, K+, Mg2+, Mn2+, Na+, Zn2+ Protein folding, where required mediated by ATP-dependent chaperone(s) [PUB_0014, PUB_0644] Trigger factor (Tig, MG_238_MONOMER) – Highly expressed protein which possibly interacts with the L23 subunit of every ribosome, co-translationally assisting in the early folding every protein [PUB_0014, PUB_0644]. Binds vacant ribosomes with half-life of 11 s [PUB_0005]; binds ribosome-peptide complexes with half-life of 15-50 s [PUB_0005]; remains associated with the peptide for a up to more seconds after peptide release from the ribosome [PUB_0005]. Trigger factor-50S ribosome affinity: KD=1 μM [PUB_0005]. We model trigger as required for the proper folding of all proteins. Chaperone (DnaK, MG_305_MONOMER) – Folds 5-18% of proteins [PUB_0014, PUB_0644]. Typically folds proteins > 30 kDa, typically in less than 2 min [PUB_0014, PUB_0644]. Binds backbone of short, linear, unfolded, hydrophobic peptide segments [PUB_0014, PUB_0644]. ATP hydrolysis and peptide release catalyzed by GrpE (MG_201_DIMER) [PUB_0014, PUB_0644]. Regulated by co-chaperone DnaJ (MG_019_DIMER) which interacts with the peptide side chains [PUB_0014, PUB_0644]. Chaperonin (GroEL, GroES, MG_392_393_21MER) – Folds 10-15% proteins by ATP-dependent mechanism [PUB_0014, PUB_0644]. Typically folds proteins 20-60 kDa in size [PUB_0014, PUB_0644] with half-life > 10 min [PUB_0014, PUB_0644], 30-60 s [PUB_0389]. In addition to chaperones, membrane protein folding may be assisted by phosphatidyl ethanolamine (PE) and phosphatidyl glycerol (PG) [PUB_0646]. This effect is not currently modeled.
  1. Eds Lund P. Molecular Chaperones in the Cell. Oxford University Press, New York (2001). WholeCell: PUB_0014, ISBN: 9780199638673

  2. Eds Pain R. Mechanisms of protein folding. Oxford University Press: USA (2000). WholeCell: PUB_0644, ISBN: 9780199637881

  3. Kaiser CM, Chang HC, Agashe VR, Lakshmipathy SK, Etchells SA, Hayer-Hartl M, Hartl FU, Barral JM. Real-time observation of trigger factor function on translating ribosomes. Nature 444, 455-60 (2006). WholeCell: PUB_0005, PubMed: 17051157

  4. Kerner MJ, Naylor DJ, Ishihama Y, Maier T, Chang HC, Stines AP, Georgopoulos C, Frishman D, Hayer-Hartl M, Mann M, Hartl FU. Proteome-wide analysis of chaperonin-dependent protein folding in Escherichia coli. Cell 122, 209-20 (2005). WholeCell: PUB_0389, PubMed: 16051146

  5. van Dalen A, de Kruijff B. The role of lipids in membrane insertion and translocation of bacterial proteins. Biochim Biophys Acta 1694, 97-109 (2004). WholeCell: PUB_0646, PubMed: 15546660

Created 2012-10-01 15:07:35
Last updated 2012-10-01 15:14:00