title: Solution structure of the albumin-binding GA module: a versatile bacterial protein domain.
abstract: The albumin-binding GA module is found in a family of surface proteins of different bacterial species. It comprises 45 amino acid residues and represents the first known example of contemporary module shuffling. Using 1H NMR spectroscopy we have determined the solution structure of the GA module from protein PAB, a protein of the anaerobic human commensal and pathogen Peptostreptococcus magnus. This structure, the first three-dimensional structure of an albumin-binding protein domain described, was shown to be composed of a left-handed three-helix-bundle. Sequence differences between GA modules with different affinities for albumin indicated that a conserved region in the C-terminal part of the second helix and the flexible sequence between helices 2 and 3 could contribute to the albumin-binding activity. The effect on backbone amide proton exchange rates upon binding to albumin support this assumption. The GA module has a fold that is strikingly similar to the immunoglobulin-binding domains of staphylococcal protein A but it shows no resemblance to the fold shared by the immunoglobulin-binding domains of streptococcal protein G and peptostreptococcal protein L. When the gene sequences, binding properties and thermal stability of these four domains are analysed in relation to their global folds an evolutionary pattern emerges. Thus, in the evolution of novel binding properties mutations are allowed only as long as the energetically favourable global fold is maintained.
authors.affiliation: Department of Physical Chemistry, Lund University, Sweden.
authors.forename: M U
authors.initials: MU
authors.lastname: Johansson
authors.forename: M
authors.initials: M
authors.lastname: de Château
authors.forename: M
authors.initials: M
authors.lastname: Wikström
authors.forename: S
authors.initials: S
authors.lastname: Forsén
authors.forename: T
authors.initials: T
authors.lastname: Drakenberg
authors.forename: L
authors.initials: L
authors.lastname: Björck
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D005075:Biological Evolution; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D003903:Deuterium / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000378:metabolism*; D012996:Solutions; D013205:Staphylococcal Protein A / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D012709:Serum Albumin; D012996:Solutions; D013205:Staphylococcal Protein A; C086961:PAB protein, Peptostreptococcus magnus; D003903:Deuterium