A number of cell-cell interactions in the nervous system are mediated byimmunoglobulin gene superfamily members. For example, neuroglian, a homophilicneural cell adhesion molecule in Drosophila, has an extracellular portion comprising six C-2 type immunoglobulin-like domains followed by five fibronectin type III (FnIII) repeats.Neuroglian shares this domain organization and significant sequence identity with Ll, amurine neural adhesion molecule that could be a functional homologue. Here I report thecrystal structure of a proteolytic fragment containing the first two FnIII repeats ofneuroglian (NgFn 1,2) at 2.0Å. The interpretation of photomicrographs of rotaryshadowed Ng, the entire extracellular portion of neuroglian, and NgFnl-5, the fiveneuroglian Fn III domains, is also discussed.
The structure of NgFn 1,2 consists of two roughly cylindrical β-barrel structural motifsarranged in a head-to-tail fashion with the domains meeting at an angle of ~120, as definedby the cylinder axes. The folding topology of each domain is identical to that previouslyobserved for single FnIII domains from tenascin and fibronectin. The domains ofNgFn1,2 are related by an approximate two fold screw axis that is nearly parallel to thelongest dimension of the fragment. Assuming this relative orientation is a general propertyof tandem FnIII repeats, the multiple tandem FnIII domains in neuroglian and otherproteins are modeled as thin straight rods with two domain zig-zag repeats. Whencombined with the dimensions of pairs of tandem immunoglobulin-like domains from CD4and CD2, this model suggests that neuroglian is a long narrow molecule (20 - 30 Å indiameter) that extends up to 370Å from the cell surface.
In photomicrographs, rotary shadowed Ng and NgFn1-5 appear to be highly flexiblerod-like molecules. NgFn 1-5 is observed to bend in at least two positions and has a meantotal length consistent with models generated from the NgFn1,2 structure. Ng molecules have up to four bends and a mean total length of 392 Å, consistent with a head-to-tailpacking of neuroglian's C2-type domains.
