The structure in solution of the second Ig-module fragment of residues 117-
208 of NCAM has been determined. Like the first Ig-module of residues 20-11
6, it belongs to the I set of the immunogloblin superfamily. Module 1 and m
odule 2 interact weakly, and the binding sites of this interaction have bee
n identified. The two-module fragment NCAM(20-208) is a stable dimer, Remov
al of the charged residues in these sites in NCAM(20-208) abolishes the dim
erization. Modeling the dimer of NCAM(20-208) to fit the interactions of th
ese charges produces one coherent binding site for the formation of two ant
iparallel strands of the first two NCAM modules. This mode of binding could
be a major element in trans-cellular interactions in neural cell adhesion.