Back تكدس البروتين Arabic Agrégation des protéines French タンパク質凝集 Japanese Eiwitaggregatie Dutch Protein agregasyonu Turkish
In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly.[1][2] Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease.[3][4]
After synthesis, proteins typically fold into a particular three-dimensional conformation that is the most thermodynamically favorable: their native state.[5] This folding process is driven by the hydrophobic effect: a tendency for hydrophobic (water-fearing) portions of the protein to shield themselves from the hydrophilic (water-loving) environment of the cell by burying into the interior of the protein. Thus, the exterior of a protein is typically hydrophilic, whereas the interior is typically hydrophobic.
Protein structures are stabilized by non-covalent interactions and disulfide bonds between two cysteine residues. The non-covalent interactions include ionic interactions and weak van der Waals interactions. Ionic interactions form between an anion and a cation and form salt bridges that help stabilize the protein. Van der Waals interactions include nonpolar interactions (i.e. London dispersion force) and polar interactions (i.e. hydrogen bonds, dipole-dipole bond). These play an important role in a protein's secondary structure, such as forming an alpha helix or a beta sheet, and tertiary structure. Interactions between amino acid residues in a specific protein are very important in that protein's final structure.
When there are changes in the non-covalent interactions, as may happen with a change in the amino acid sequence, the protein is susceptible to misfolding or unfolding. In these cases, if the cell does not assist the protein in re-folding, or degrade the unfolded protein, the unfolded/misfolded protein may aggregate, in which the exposed hydrophobic portions of the protein may interact with the exposed hydrophobic patches of other proteins.[6][7] There are three main types of protein aggregates that may form: amorphous aggregates, oligomers, and amyloid fibrils.[8]
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- ^ Stefani M, Dobson CM (November 2003). "Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution". Journal of Molecular Medicine. 81 (11): 678–699. doi:10.1007/s00109-003-0464-5. PMID 12942175. S2CID 23544974.
- ^ De Felice FG, Vieira MN, Meirelles MN, Morozova-Roche LA, Dobson CM, Ferreira ST (July 2004). "Formation of amyloid aggregates from human lysozyme and its disease-associated variants using hydrostatic pressure". FASEB Journal. 18 (10): 1099–1101. doi:10.1096/fj.03-1072fje. PMID 15155566. S2CID 13647147.
- ^ Tanzi RE, Bertram L (February 2005). "Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective". Cell. 120 (4): 545–555. doi:10.1016/j.cell.2005.02.008. PMID 15734686. S2CID 206559875.
- ^ Brüning A, Jückstock J (2015-01-01). "Misfolded proteins: from little villains to little helpers in the fight against cancer". Frontiers in Oncology. 5: 47. doi:10.3389/fonc.2015.00047. PMC 4338749. PMID 25759792.
- ^ Gething MJ, Sambrook J (January 1992). "Protein folding in the cell". Nature. 355 (6355): 33–45. Bibcode:1992Natur.355...33G. doi:10.1038/355033a0. PMID 1731198. S2CID 4330003.
- ^ Roberts CJ (December 2007). "Non-native protein aggregation kinetics". Biotechnology and Bioengineering. 98 (5): 927–938. doi:10.1002/bit.21627. PMID 17705294. S2CID 21787377.
- ^ Cox DL, Nelson MM (2013). Lehninger Principles of Biochemistry. New York: W.H. Freeman. p. 143. ISBN 978-1-4292-3414-6.