J. Iran. Chem. Soc., Vol. 7, No. 3 September 2010, pp.521~544.

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Protein-Protein Interactions Leading to Aggregation: Perspectives on Mechanism, Significance and Control

A. Ebrahim-Habibia,b, D. Morshedic,b, N. Rezaei-Ghalehb, M. Sabbaghiand,b, M. Nemat-Gorganib,e,*

aEndocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran
bInstitute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
cIndustrial and Environmental Biotechnology Department, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
dDepartment of Andrology, Reproductive Medicine Research Center, Royan Institute, ACECR, Tehran, Iran eStanford Genome Technology Center, Stanford University, Palo Alto, CA, USA

Protein aggregates, whether amorphous or structured (amyloid), have attracted much attention in recent years and despite extensive efforts, the mechanism of their formation is poorly understood. While ”natural” aggregation (polymerization) of monomers could  improve the biological function of  some proteins, it is usually the darker side of this phenomenon which is discussed in many studies: deleterious aggregation that could lead to loss of biological activity under in vitro conditions or cause misfolding diseases. In this review, protein aggregation has been overviewed, starting from some general concepts involved in its formation, followed by mentioning studies aimed at elucidation of its kinetics and mechanism, or characterization of intermediates that would be aggregation-prone, and finally, reporting some of the studies related to the design of methods that would control the process. Similarly, amyloid aggregates have been defined, and current methods used in their characterization have been briefly described, with an emphasis on in silico studies. Finally, identification and design of such molecules which may be effective in control of this process is discussed.

Keywords: Aggregation, Amyloid, Protein, Interaction, Chemical modification, Small molecules

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