Structural analysis and evolution of specificity of the SUMO UFD E1-E2 interactions.
SUMO belongs to the ubiquitin-like family (UbL) of protein modifiers. SUMO is conserved among eukaryotes and is essential for the regulation of processes such as DNA damage repair, transcription, DNA replication and mitosis. UbL modification of proteins occurs via a specific enzymatic cascade formed by the crosstalk between the E1-activating enzyme, the E2-conjugating enzyme and the E3-ligase. An essential discrimination step in all UbL modifiers corresponds to the interaction between E1 and E2 enzymes, which is mediated by the recruitment of the E2 to the UFD domain (Ubiquitin-Fold Domain) of the E1 enzyme. To gain insights in the properties of this interface, we have compared the structures of the complexes between E1 UFD domain and E2 in human and yeast, revealing two alternative UFD platforms that interact with a conserved E2. Comparative sequence analysis of the E1 UFD domain indicates that the E2 binding region has been conserved across phylogenetic closely related species, in which higher sequence conservation can be found in the E2 binding region than in the entire UFD domain. These distinctive strategies for E1-E2 interactions through the UFD domain might be the consequence of a high selective pressure to ensure specificity of each modifier conjugation system.
Institut de Biotecnologia i de Biomedicina, Departament de Bioquimica i Biologia Molecular, Serra Hunter Fellow, Universitat Autonoma de Barcelona, 08193 Barcelona, Bellaterra, Spain.
Bing
B
Liu
Center for Research in Agricultural Genomics-CRAG, Edifici CRAG-Campus UAB, Bellaterra 08193 Barcelona, Spain.
L Maria
LM
Lois
Institut de Biotecnologia i de Biomedicina, Departament de Bioquimica i Biologia Molecular, Serra Hunter Fellow, Universitat Autonoma de Barcelona, 08193 Barcelona, Bellaterra, Spain.
David
D
Reverter
D000595:Amino Acid Sequence; D002384:Catalysis; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D017385:Sequence Homology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry* / Q000378:metabolism*; D044764:Ubiquitin-Activating Enzymes / Q000737:chemistry* / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry* / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D044764:Ubiquitin-Activating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9