Tetraspanin forms a rigid structure.

Tetraspanin contains a tightly packed quartet of transmembrane helices, according to a new, high resolution electron microscopy structure deduced by Min et al. (page 975). The rigid tetraspanin proteins may thus act as stable pilings in a lipid sea, say the authors.

Tetraspanins associate with a number of important transmembrane proteins such as integrins to form distinct signaling networks, called tetraspanin webs. Lipids trapped in the networks create microdomains with characteristic compositions and unique properties.

The web under study here was made up of uroplakins. Two uroplakin tetraspanins each pair with a single transmembrane partner forming a heterotetramer subunit, six of which then form a 16-nm wide, ring-shaped particle. A two-dimensional crystalline array of these particles contributes to a remarkable urothelial permeability barrier, which keeps urine on one side and body fluid on the other.

These arrays are particularly suitable for electron microscopic studies. At 6 Å resolution, the team could assign secondary structures to certain regions of the particle. The angle between membrane-traversing α-helices is minimal, so that the helices can pack tightly together. Each single transmembrane partner is shaped like an L that covers the tetraspanins and connects to a neighboring subunit.

The relatively rigid tetraspanin structure is ideal for docking other tall signaling transmembrane proteins. Tetraspanins can also help these proteins to pass messages into the cell, and are themselves the receptors and signaling conduits for some bacteria and viruses. Future structural studies should reveal how these signals are transduced to trigger a wide variety of cellular responses.