Gene product (gp) 24 of bacteriophage T4 forms the pentameric vertices of the capsid. Using x-ray crystallography, we found the principal domain of gp24 to have a polypeptide fold similar to that of the HK97 phage capsid protein plus an additional insertion domain. Fitting gp24 monomers into a cryo-EM density map of the mature T4 capsid suggests that the insertion domain interacts with a neighboring subunit, effecting a stabilization analogous to the covalent crosslinking in the HK97 capsid. Sequence alignment and genetic data show that the folds of gp24 and the hexamer-forming capsid protein, gp23*, are similar. Accordingly, models of gp24* pentamers, gp23* hexamers, and the whole capsid were built, based on a cryo-EM image reconstruction of the capsid. Mutations in gene 23 that affect capsid shape map to the capsomer's periphery, whereas mutations that allow gp23 to substitute for gp24 at the vertices modify the interactions between monomers within capsomers. Structural data show that capsid proteins of most tailed phages, and some eukaryotic viruses, may have evolved from a common ancestor.evolution ͉ gene product 24 ͉ major capsid protein T he protein shells of viral capsids are remarkably stable, yet dynamic structures. They have to protect the genome during its transfer between hosts, withstand the high pressure of the condensed nucleic acid, and be able to release the genome once a susceptible host has been recognized. To reconcile both stability and dynamic requirements, assembled procapsids of many viruses undergo large conformational changes during genome packaging and maturation (1).The capsid of the dsDNA tailed bacteriophage T4 is a prolate icosahedron ( Fig. 1) whose capsomers form a T end ϭ 13 laevo hexagonal lattice in the end caps and a T mid ϭ 20 lattice in the cylindrical midsection (2). The protein shell consists of the major capsid protein gene product (gp) 23*, the pentameric vertex protein gp24*, the portal protein or ''connector'' gp20, and the two accessory proteins, gp hoc (highly antigenic outer capsid protein) and gp soc (small outer capsid protein) (3), that decorate the outside of the shell. The dodecameric connector replaces a pentamer of gp24* at one of the 12 vertices and serves as a special portal for DNA packaging, tail attachment, and DNA exit (4, 5).During procapsid assembly, gp23, gp24, and gp20 form a shell around the core structure composed primarily of the scaffolding protein gp22 and assembly protease gp21 (3). The protease activates once procapsid assembly has been completed and cleaves the proteins of the core into small peptides, most of which leave the maturing procapsid, freeing space for the genome. The gp21 protease also cleaves a 65-residue-long, amino-terminal fragment from the 56-kDa gp23, generating the 48.7-kDa gp23* (3). In addition, the 10-residue, amino-terminal region of the 48.7-kDa gp24 is cleaved, giving rise to the 47.6-kDa gp24* (3). These cleavages trigger a large conformational rearrangement in the procapsid, resulting in expansion and causing the ...

Human S100A7 (psoriasin) is overexpressed in inflammatory diseases. The recently discovered, co-evolved hS100A15 is almost identical in sequence and up-regulated with hS100A7 during cutaneous inflammation. The functional role of these closely related proteins for inflammation remains undefined. By generating specific Abs, we demonstrate that hS100A7 and hS100A15 proteins are differentially expressed by specific cell types in the skin. Although highly homologous, both proteins are chemoattractants with distinct chemotactic activity for leukocyte subsets. We define RAGE (receptor for advanced glycation end products) as the hS100A7 receptor, whereas hS100A15 functions through a Gi protein-coupled receptor. hS100A7-RAGE binding, signaling, and chemotaxis are zinc-dependent in vitro, reflecting the previously reported zinc-mediated changes in the hS100A7 dimer structure. When combined, hS100A7 and hS100A15 potentiate inflammation in vivo. Thus, proinflammatory synergism in disease may be driven by the diverse biology of these almost identical proteins that have just recently evolved. The identified S100A7 interaction with RAGE may provide a novel therapeutic target for inflammation.