The GroE proteins (the terms “GroEL” and “GroES” just indicate “large” and “small”) are the major class of chaperonin (ring-shaped molecular chaperones/ heat shock proteins) found in bacteria.  In mammals these are replaced by the related CCT or TRiC machinery.  This article provides a glimpse into how these guys are helpful for protein folding.  Basically they form cages around the proteins so that they can do their thing, protected from the chaotic cellular environment (crowding, protein-protein collisions with high kinetic energy, etc.)  Also apparently in addition to providing isolation, the cages  have some chemical properties that  promote proper folding.

“Structural features of the GroEL-GroES nano-cage required for rapid folding of encapsulated protein,” Tang et al., Cell (2006)

  • GroEL and GroES form chaperonin nano-cages around proteins, allowing them to fold in isolation
  • Confinement theory: volume affects speed
    • Small proteins (under 30 kDa) fold more rapidly in a smaller cage (down to the point where the restriction is too much, and slowed folding dramatically)
    • Larger proteins (40-50 kDa) show slower folding when cage size is either expanded or reduced
    • Other factors also seem to influence folding speed:
      • Interactions with C-terminal, mildly hydrophobic Gly-Gly-Met repeat sequence of GroEL that protrudes into the cavity
      • Repulsion effects from the negatively charged cavity wall
      • The combination of these factors provides an evolutionarily optimized physical environment for complex folding
  • “An additional important role of cage-mediated annealing is to preserve the foldability of a protein despite the presence of mutations, as shown for MBP.  This capacity would explain the recent finding that overproduction of GroEL/GroES reduces the phenotypic penetrance of deleterious mutations in bacterial cell lineages (Maisnier-Patin et al., 2005) in a manner comparable to the conformational buffering effects proposed for other chaperone systems (Rutherford and Lindquist, 1998).”