An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

TY - JOUR

T1 - An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

AU - Wong, Jaslyn E M M

AU - Midtgaard, Søren Roi

AU - Gysel, Kira

AU - Thygesen, Mikkel B

AU - Sørensen, Kasper K

AU - Jensen, Knud J

AU - Stougaard, Jens

AU - Thirup, Søren

AU - Blaise, Mickaël

PY - 2015/3

Y1 - 2015/3

N2 - LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

AB - LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

U2 - 10.1107/S139900471402793X

DO - 10.1107/S139900471402793X

M3 - Journal article

C2 - 25760608

SN - 2059-7983

VL - 71

SP - 592

EP - 605

JO - Acta crystallographica Section D: Structural biology

JF - Acta crystallographica Section D: Structural biology

IS - Pt 3

ER -