The T4-encoded cochaperonin, gp31, has unique properties that explain its requirement for the folding of the T4 major capsid protein.

The morphogenesis of bacteriophage T4 requires a specialized bacteriophage-encoded molecular chaperone (gp31) that is essential for the folding of the T4 major capsid protein (gp23). gp31 is related to GroES, the chaperonin of the Escherichia coli host because it displays a similar overall structure and properties. Why GroES is unable to fold the T4 capsid protein in conjunction with GroEL is unknown. Here we show that gp23 binds to the GroEL heptameric ring opposite to the ring that is bound by gp31 (the so-called trans-ring), while no binding to the trans-ring of the GroEL-GroES complex is observed. Although gp23 can be enclosed within the folding cage of the GroEL-gp31 complex, encapsulation within the GroEL-GroES complex is not possible. So it appears that folding of the T4 major capsid protein requires a gp31-dependent cis-folding mechanism likely inside an enlarged "Anfinsen cage" provided by GroEL and gp31.