From Protein Structure to Function with Bioinformatics.pdf

Chapter 6Function Diversity Within Foldsand SuperfamiliesBenoit H. Dessailly and Christine A. OrengoAbstract With the advent of structural genomics initiatives, increasing numbersof three-dimensional structures are available for proteins of unknown function.However, the extent to which structural information helps understanding function isstill a matter of debate. Here, the value of detecting structural relationships at differentlevels (typically, fold and superfamily) for transferring functional annotationsbetween proteins is reviewed. First, function diversity of proteins sharing the samefold is investigated, and it is shown that although the identification of a fold can insome cases provide clues on functional properties, the diversity of functions withina fold can be such that this information is very limited for some particularly diversefolds (e.g. super-folds). Next, since structural data can help detecting homologyin the absence of sequence similarity, function diversity between proteins fromthe same superfamily (homologous proteins) is analysed. The evolutionary causesand the mechanisms that have generated the observed functional diversity betweenrelated proteins are discussed, and helpful tools for the correlated analysis of structure,function and evolution are reviewed.6.1 Defining FunctionBefore discussing how the detection of fold or superfamily relationships can helpdetermining the function of a protein, it is necessary to define clearly the meaningof the term function in this chapter and, in particular, to delineate the aspects offunction that can be inferred best using structural information.Function is a relatively vague concept that covers many different aspects of the activityof a protein. Furthermore, the aspects covered by that single word vary with the differentfields of protein science. For example, a physiologist may describe the functionof a protein in terms of its impact on the global phenotype (e.g. “inducer of cell death”),B.H. Bessailly and C.A. Orengo*Department of Structural and Molecular Biology, University College London,London WC1E 6BT, UK*Corresponding author: e-mail: orengo@biochemistry.ucl.ac.ukD.J. Rigden (ed.) From Protein Structure to Function with Bioinformatics, 143© Springer Science + Business Media B.V. 2009