L. Shapiro et al., CONSIDERATIONS ON THE FOLDING TOPOLOGY AND EVOLUTIONARY ORIGIN OF CADHERIN DOMAINS, Proceedings of the National Academy of Sciences of the United Statesof America, 92(15), 1995, pp. 6793-6797
Cell-cell adhesion in zonula adherens and desmosomal junctions is medi
ated by cadherins, and recent crystal structures of the first domain f
rom murine N-cadherin provide a plausible molecular basis for this adh
esive action. A structure-based sequence analysis of this adhesive dom
ain indicates that its fold is common to all extracellular cadherin do
mains. The cadherin folding topology is also shown to be similar to im
munoglobulin-like domains and to other Greek-key beta-sandwich structu
res, as diverse as domains from plant cytochromes, bacterial cellulase
s, and eukaryotic transcription factors. Sequence similarities between
cadherins and these other molecules are very low, however, and intron
patterns are also different. On balance, independent origins for a fa
vorable folding topology seem more likely than evolutionary divergence
from an ancestor common to cadherins and immunoglobulins.