Crystal structure of a mucus-binding protein repeat reveals an unexpected functional immunoglobulin binding activity.
Lactobacillus reuteri mucus-binding protein (MUB) is a cell-surface protein that is involved in bacterial interaction with mucus and colonization of the digestive tract. The 353-kDa mature protein is representative of a broadly important class of adhesins that have remained relatively poorly characterized due to their large size and highly modular nature. MUB contains two different types of repeats (Mub1 and Mub2) present in six and eight copies, respectively, and shown to be responsible for the adherence to intestinal mucus. Here we report the 1.8-A resolution crystal structure of a type 2 Mub repeat (184 amino acids) comprising two structurally related domains resembling the functional repeat found in a family of immunoglobulin (Ig)-binding proteins. The N-terminal domain bears striking structural similarity to the repeat unit of Protein L (PpL) from Peptostreptococcus magnus, suggesting binding in a non-immune Fab-dependent manner. A distorted PpL-like fold is also seen in the C-terminal domain. As with PpL, Mub repeats were able to interact in vitro with a large repertoire of mammalian Igs, including secretory IgA. This hitherto undetected activity is consistent with the current model that antibody responses against commensal flora are of broad specificity and low affinity.
MacKenzie
Donald A
DA
Institute of Food Research, Colney Lane, Norwich NR4 7UA, United Kingdom.
Tailford
Louise E
LE
Hemmings
Andrew M
AM
Juge
Nathalie
N
D018829:Adhesins, Bacterial / Q000737:chemistry*; D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray / Q000379:methods; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D052200:Limosilactobacillus reuteri / Q000378:metabolism*; D008969:Molecular Sequence Data; D009093:Mucus / Q000378:metabolism*; D010462:Peptostreptococcus / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D018829:Adhesins, Bacterial; D007136:Immunoglobulins