TY - JOUR

T1 - Short arm region of laminin-5 gamma2 chain: structure, mechanism of processing and binding to heparin and proteins.

AU - Sasaki, T

AU - Göhring, W

AU - Mann, K

AU - Brakebusch, C

AU - Yamada, Y

AU - Fässler, R

AU - Timpl, R

N1 - Keywords: Amino Acid Sequence; Animals; Bone Morphogenetic Proteins; Calcium-Binding Proteins; Cell Adhesion Molecules; Cell Line; Disulfides; Esophagus; Extracellular Matrix Proteins; Heparin; Humans; Immune Sera; Isomerism; Ligands; Membrane Glycoproteins; Metalloendopeptidases; Mice; Molecular Sequence Data; Molecular Weight; Protein Binding; Protein Processing, Post-Translational; Protein Subunits; Rabbits; Skin; Structure-Activity Relationship; Surface Plasmon Resonance

PY - 2001

Y1 - 2001

N2 - Laminin-5 is a typical component of several epithelial tissues and contains a unique gamma2 chain which can be proteolytically processed by BMP-1. This occurs in the N-terminal half of the gamma2 chain (606 residues), which consists of two rod-like tandem arrays of LE modules, LE1-3 and LE4-6, that flank a globular L4m module containing the cleavage site. Recombinant analysis of L4m, which includes an additional imperfect LE module essential for proper folding, demonstrated an unusual pattern of disulfide bonding. These connectivities prevented the release of gamma2LE1-3L4 m after BMP-1 cleavage which required in addition disulfide reshuffling by isomerases. The liberated segment bound through its L4 m module to heparin, nidogen-1, fibulin-1 and fibulin-2. A further heparin/sulfatide-binding site could be attributed to some arginine residues in module LE1. The gamma2LE4-6 segment remaining in processed laminin-5 showed only a strong binding to fibulin-2. Immunological studies showed a similar partial processing in cell culture and tissues and the persistence of the released fragment in tissues. This indicated that both N-terminal regions of the gamma2 chain may have a function in vivo.

AB - Laminin-5 is a typical component of several epithelial tissues and contains a unique gamma2 chain which can be proteolytically processed by BMP-1. This occurs in the N-terminal half of the gamma2 chain (606 residues), which consists of two rod-like tandem arrays of LE modules, LE1-3 and LE4-6, that flank a globular L4m module containing the cleavage site. Recombinant analysis of L4m, which includes an additional imperfect LE module essential for proper folding, demonstrated an unusual pattern of disulfide bonding. These connectivities prevented the release of gamma2LE1-3L4 m after BMP-1 cleavage which required in addition disulfide reshuffling by isomerases. The liberated segment bound through its L4 m module to heparin, nidogen-1, fibulin-1 and fibulin-2. A further heparin/sulfatide-binding site could be attributed to some arginine residues in module LE1. The gamma2LE4-6 segment remaining in processed laminin-5 showed only a strong binding to fibulin-2. Immunological studies showed a similar partial processing in cell culture and tissues and the persistence of the released fragment in tissues. This indicated that both N-terminal regions of the gamma2 chain may have a function in vivo.

U2 - 10.1006/jmbi.2001.5176

DO - 10.1006/jmbi.2001.5176

M3 - Journal article

C2 - 11733994

VL - 314

SP - 751

EP - 763

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -