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Genomics

Functional links between proteins

Nature volume 402, pages 23–26 (1999)Cite this article

The critical information needed to construct useful models of pathways and assemblies is provided by experiment, most importantly by proteomics and structural biology. Proteomics aims to identify and characterize complete sets of proteins and protein–protein interactions. It involves large-scale approaches such as the yeast two-hybrid system, mass spectrometry, two-dimensional gel electrophoresis and DNA-microarray hybridization3. The size and complexity of the task can be appreciated by assuming between five and 50 functional links per protein, resulting in 30,000 to 300,000 links for a single yeast cell. Although experiments have characterized about 30% of yeast proteins, they are sometimes not rapid, inexpensive or complete enough. So there is a need to assign function using computational methods.

Computational methods have traditionally assigned function by sequence similarity to a characterized protein4,5. Such annotation is possible because evolution produced families of homologous proteins that share a common ancestor, and thus have similar sequences, structures and, often, functions. Protein comparisons have allowed some insight into the function of another 30% of yeast proteins6. However, functional assignment by homology is limited by two factors. First, it can be applied only to proteins with detectable homologues of known function. Second, it is not always clear what functional properties are shared by the matched proteins, especially for the more distant matches.

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Figure 1: Functional annotation by computation.

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  1. the Laboratories of Molecular Biophysics, Pels Family Center for Biochemistry and Structural Biology, The Rockefeller University, 1230 York Avenue, New York, 10021, New York, USA

    Andrej Šali

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Šali, A. Functional links between proteins. Nature 402, 23–26 (1999). https://doi.org/10.1038/46915

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