title: A core mutation affecting the folding properties of a soluble domain of the ATPase protein CopA from Bacillus subtilis.
abstract: The two N-terminal domains of the P-type copper ATPase, CopAa and CopAb, from Bacillus subtilis differ in their folding capabilities in vitro. Whereas CopAb has the typical betaalphabetabetaalphabeta structure and is a rigid protein, CopAa is found to be largely unfolded. A sequence analysis of the two and of orthologue homologous proteins indicates that Ser46 in CopAa may destabilise the hydrophobic core, as also confirmed through a bioinformatic energy study. CopAb has a Val in the corresponding position. The S46V and S46A mutants are found to be folded, although the latter displays multiple conformations. S46VCopAa, in both apo and copper(I) loaded forms, has very similar structural and dynamic properties with respect to CopAb, besides a different length of strand beta2 and beta4. It is intriguing that the oxygen of Thr16 is found close, though at longer than bonding distance, to copper in both domains, as it also occurs in a human orthologue domain. This study contributes to understanding the behaviour of proteins that do not properly fold in vitro. A possible biological significance of the peculiar folding behaviour of this domain is discussed.
authors.affiliation: Department of Chemistry, The Magnetic Resonance Center CERM, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Banci
authors.forename: Ivano
authors.initials: I
authors.lastname: Bertini
authors.forename: Simone
authors.initials: S
authors.lastname: Ciofi-Baffoni
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gonnelli
authors.forename: Xun-Cheng
authors.initials: XC
authors.lastname: Su
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry*; D003001:Cloning, Molecular; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry; D013696:Temperature; D014633:Valine / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C071263:CopA protein, Bacteria; D012694:Serine; D000251:Adenosine Triphosphatases; D014633:Valine