RESUMEN
While the slipknot topology in proteins has been known for over a decade, its evolutionary origin is still a mystery. We have identified a previously overlooked slipknot motif in a family of two-domain membrane transporters. Moreover, we found that these proteins are homologous to several families of unknotted membrane proteins. This allows us to directly investigate the evolution of the slipknot motif. Based on our comprehensive analysis of 17 distantly related protein families, we have found that slipknotted and unknotted proteins share a common structural motif. Furthermore, this motif is conserved on the sequential level as well. Our results suggest that, regardless of topology, the proteins we studied evolved from a common unknotted ancestor single domain protein. Our phylogenetic analysis suggests the presence of at least seven parallel evolutionary scenarios that led to the current diversity of proteins in question. The tools we have developed in the process can now be used to investigate the evolution of other repeated-domain proteins.
Asunto(s)
Antiportadores , Evolución Molecular , Secuencias de Aminoácidos , Antiportadores/química , Antiportadores/genética , Antiportadores/metabolismo , Biología Computacional , Bases de Datos de Proteínas , Filogenia , Conformación ProteicaRESUMEN
The 'Genus for biomolecules' database (http://genus.fuw.edu.pl) collects information about topological structure and complexity of proteins and RNA chains, which is captured by the genus of a given chain and its subchains. For each biomolecule, this information is shown in the form of a genus trace plot, as well as a genus matrix diagram. We assemble such information for all and RNA structures deposited in the Protein Data Bank (PDB). This database presents also various statistics and extensive information about the biological function of the analyzed biomolecules. The database is regularly self-updating, once new structures are deposited in the PDB. Moreover, users can analyze their own structures.