Analysis of structural similarities between brain Thy-1 antigen and immunoglobulin domains. Evidence for an evolutionary relationship and a hypothesis for its functional significance

Abstract

The Thy-1 cell membrane glycoprotein from rat brain has structural and sequence homologies with Ig domains. The 2 disulfide bonds of Thy-1 are consistent with the Ig-fold. The molecule contains extensive .beta.-structure as shown by the circular dichroism spectrum. Secondary structure prediction locates .beta.-strands along the sequence in a manner consistent with the Ig-fold. Based on rules derived from known .beta.-sheet structures, a 3-dimensional structure with the Ig-fold is predicted as favorable for Thy-1.5. Sequences in the proposed .beta.-strands of Thy-1 and known .beta.-strands of Ig domains show significant sequence homology. This homology is statistically more significant than for the comparison of proposed .beta.-strand sequences of .beta.2-microglobulin with Ig domains. A hypothesis is presented for the possible functional significance of an evolutionary relationship between Thy-1 and Ig. Both Thy-1 and Ig probably evolved from primitive molecules, with an Ig-fold, which mediated cell-cell interactions. The present-day role of Thy-1 may be similar to that of the primitive domain.