Structural analysis of the murine cell adhesion molecule L1 by electron microscopy and computer-assisted modelling.
In the present study we have analysed the morphology of two fragments with apparent molecular weights of 180 and 140 kDA (L1-180 and L1-140) derived from the extracellular region of the murine neural cell adhesion molecule L1. The fragment L1-180 consists of almost the entire extracellular part of the molecule, and is built up of six immunoglobulin-like and five fibronectin type III-like domains. Fragment L1-140 lacks one-half of the third, the fourth and the fifth fibronectin type III-like domains. By electron microscopic analysis of rotary-shadowed molecules, L1-140 and L1-180 revealed fibrillar structures 31-43 nm long and 7-12 nm wide with one pronounced globular terminal domain. As determined by complex formation with an L1 antibody, this terminal part of the molecule is formed by the fibronectin type III-like domains. The individual structures showed variation and complexity, and four distinct aspects were identified. These different forms probably represent two-dimensional projections of the same three-dimensional helical structure. Computer-assisted modelling of the L1 molecule, i.e. the protein backbone, showed no strong intramolecular interaction between the different fibronectin type III- or Ig-like domains, suggesting that the formation of the globular part of the molecule is probably achieved by protein-carbohydrate and/or carbohydrate-carbohydrates rather than protein-protein interactions. In addition, our model proposes that interactions occur within the interfaces between the different domains. The highly conserved amino acid residues in these regions point to the necessity of maintaining the orientation between the different domains.
Drescher
B
B
Molekulare Biophysik 1, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Spiess
E
E
Schachner
M
M
Probstmeier
R
R
D000818:Animals; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure*; D051379:Mice; D008854:Microscopy, Electron; D008961:Models, Structural; D010446:Peptide Fragments / Q000302:isolation & purification
D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D010446:Peptide Fragments