Competition between protein aggregation and protein complex formation
© Pechmann et al; licensee BioMed Central Ltd 2008
Published: 30 October 2008
Interactions between proteins are vital for essentially every process in a living cell. Physico-chemical complementarity, which can be considered as the driving force for molecular recognition, has been found to not consistently explain protein-ligand interactions. As aberrant interactions should be avoided in order to maintain cell viability, promoting complex formation and preventing protein aggregation are two opposite requirements on the physico-chemical properties of protein surfaces.
As a first step, aggregation propensity profiles were calculated using the Zyggregator algorithm [1–3], which takes hydrophobicity, charge, structural propensities and alternating hydrophobic-polar patterns into account. Positive peaks in these profiles indicate regions that promote aggregation while negative peaks identify regions preventing aggregation. These calculations are based on individual aggregation propensities for each amino acid based on their physico-chemical properties and experimentally determined [1–3]. The aggregation propensity profiles were then mapped onto the structures of protein complexes  and aggregation propensity patches of interfaces and surfaces were compared.
The specificity in molecular recognition is achieved through a combination of positive and negative design principles, which, respectively, promote the assembly of functional complexes and prevent the formation of potentially dangerous aggregates.
The molecules in the figure were rendered using PyMOL (W.L. DeLano, http://pymol.sourceforge.net/).
- DuBay KF, Pawar AP, Chiti F, Zurdo J, Dobson CM, Vendruscolo M: Prediction of the absolute aggregation rates of amyloidogenic polypeptide chains. J Mol Biol 2004, 341(5):1317–26. 10.1016/j.jmb.2004.06.043View ArticlePubMedGoogle Scholar
- Pawar AP, Dubay KF, Zurdo J, Chiti F, Vendruscolo M, Dobson CM: Prediction of "aggregation-prone" and "aggregation-susceptible" regions in proteins associated with neurodegenerative diseases. J Mol Biol 2005, 350(2):379–92. 10.1016/j.jmb.2005.04.016View ArticlePubMedGoogle Scholar
- Tartaglia GG, Pawar AP, Campioni S, Dobson CM, Chiti F, Vendruscolo M: Prediction of aggregation-prone regions in structured proteins. J Mol Biol 2008, 380(2):425–36. 10.1016/j.jmb.2008.05.013View ArticlePubMedGoogle Scholar
- Levy ED, Pereira-Leal JB, Chothia C, Teichmann SA: 3D complex: a structural classification of protein complexes. PLoS Comput Biol 2006, 2(11):e155. 10.1371/journal.pcbi.0020155PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd.