title: Thermal and chemical stability of two homologous POZ/BTB domains of KCTD proteins characterized by a different oligomeric organization.
abstract: POZ/BTB domains are widespread modules detected in a variety of different biological contexts. Here, we report a biophysical characterization of the POZ/BTB of KCTD6, a protein that is involved in the turnover of the muscle small ankyrin-1 isoform 5 and, in combination with KCTD11, in the ubiquitination and degradation of HDAC1. The analyses show that the domain is a tetramer made up by subunits with the expected α /β structure. A detailed investigation of its stability, carried out in comparison with the homologous pentameric POZ/BTB domain isolated from KCTD5, highlights a number of interesting features, which are shared by the two domains despite their different organization. Their thermal/chemical denaturation curves are characterized by a single and sharp inflection point, suggesting that the denaturation of the two domains is a cooperative two-state process. Furthermore, both domains present a significant content of secondary structure in their denatured state and a reversible denaturation process. We suggest that the ability of these domains to fold and unfold reversibly, a property that is somewhat unexpected for these oligomeric assemblies, may have important implications for their biological function. Indeed, these properties likely favor the formation of heteromeric associations that may be essential for the intricate regulation of the processes in which these proteins are involved.
authors.affiliation: Istituto di Cristallografia, CNR, Via G. Amendola 122/O, 70126 Bari, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Pirone
authors.forename: Carla
authors.initials: C
authors.lastname: Esposito
authors.forename: Stefania
authors.initials: S
authors.lastname: Correale
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Graziano
authors.forename: Sonia
authors.initials: S
authors.lastname: Di Gaetano
authors.forename: Luigi
authors.initials: L
authors.lastname: Vitagliano
authors.forename: Emilia
authors.initials: E
authors.lastname: Pedone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D008027:Light; D015221:Potassium Channels / Q000737:chemistry; D011489:Protein Denaturation; D055503:Protein Multimerization; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012542:Scattering, Radiation; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013050:Spectrometry, Fluorescence; D013696:Temperature; D014508:Urea / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C521187:KCTD5 protein, human; C559190:KCTD6 proetin, human; D015221:Potassium Channels; D014508:Urea