Cullin 3 Recognition Is Not a Universal Property among KCTD Proteins

• DOI: 10.1371/journal.pone.0126808
• Publication Date: 2015-05-14T18:06:10Z
• Authors: Giovanni Smaldone; Luciano Pirone; Nicole Balasco; Sonia Di Gaetano; Emilia Maria Pedone; Luigi Vitagliano
• Keywords: Cullin

Cullin 3 (Cul3) recognition by BTB domains is a key process in protein ubiquitination. Among Cul3 binders, great attention currently devoted to KCTD proteins, which are implicated fundamental biological processes. On the basis of high similarity these it has been suggested that ability bind could be general property among all KCTDs. In order gain new insights into functionality, we here evaluated and/or quantified binding known involved either cullin-independent (KCTD12 and KCTD15) or cullin-mediated (KCTD6 KCTD11) activities. Our data indicate KCTD6BTB KCTD11BTB with affinity forming stable complexes 4:4 stoichiometries. Conversely, KCTD12BTB KCTD15BTB do not interact Cul3, despite level sequence identity cullin Intriguingly, comparative analyses capability proteins recognize lost more than once distinct events along evolution. Present findings also provide interesting clues on structural determinants Cul3-KCTD recognition. Indeed, characterization chimeric variant KCTD11 demonstrates swapping α2β3 loop between sufficient abolish Cul3. Finally, present findings, previous literature data, virtually complete coverage members entire family.