结构生物学sturcture biology explore-46.pdfVIP

400 Evolution of protein structures and functions Lisa N Kinch* and Nick V Grishin? Within the ever-expanding repertoire of known protein basic local alignment search tool) and hidden Markov sequences and structures, many examples of evolving three- model based algorithms such as HMMER provide the dimensional structures are emerging that illustrate the plasticity most straightforward evidence of homology. Substantial and robustness of protein folds. The mechanisms by which similarities in three-dimensional structure may exist in the protein folds change often include the fusion of duplicated absence of significant sequence identity. However, domains, followed by divergence through mutation. Such because similar folds can arise independently in evolution, changes reflect both the stability of protein folds and the structural similarity alone does not provide sufficient requirements of protein function. evidence of common ancestry. In this case, evaluation of evolutionary relatedness must include additional consider- Addresses ations, such as similarity of molecular function, retention of Howard Hughes Medical Institute and Department of Biochemistry, unusual structural features, a common domain organization University of Texas Southwestern Medical Center, 5323 Harry Hines or a combination of these features. Finally, methods have Boulevard, Dallas, TX 75390-9050, USA been employed to detect small, localized regions of *e-mail: lkinch@chop.swmed.edu ?e-mail: grishin@chop.swmed.edu sequence and/or structural similarity. The evolutionary meaning of these types of similarities remains ambiguous Current Opinion in Structural Biology 2002, 12:400–408 and arguments can support either convergent or divergent 0959-4