TY - JOUR

T1 - Solution structure of the albumin-binding GA module

T2 - a versatile bacterial protein domain

AU - Johansson, Mai-Britt

AU - de Château, M

AU - Wikström, M

AU - Forsén, S

AU - Drakenberg, T

AU - Björck, L

PY - 1997/3/14

Y1 - 1997/3/14

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Bacterial Proteins

KW - Binding Sites

KW - Biological Evolution

KW - Carrier Proteins

KW - Cell Wall

KW - Conserved Sequence

KW - Deuterium

KW - Magnetic Resonance Spectroscopy

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Peptide Fragments

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Recombination, Genetic

KW - Sequence Homology, Amino Acid

KW - Serum Albumin

KW - Solutions

KW - Staphylococcal Protein A

U2 - 10.1006/jmbi.1996.0856

DO - 10.1006/jmbi.1996.0856

M3 - Journal article

C2 - 9086265

VL - 266

SP - 859

EP - 865

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 5

ER -