SBS-713 Archaea, the third domain of life

Protein Folding Systems of Archaea

Dr. Mehwish Aslam

Chaperones
• Chaperones present in Archaea are similar in function to chaprone protein
families of Eucarya, including
• Prefoldins
• Small Heat Shock Proteins (sHSPs)
• ATP-dependent chaperonins
• Hsp70 proteins and TF are generally missing from the Archaeal kingdom but
some archaea have acquired Hsp70
• Archaeal Prefoldin has been shown to have ATP-independent chaperone
properties similar to that of Hsp70 in a folding pathway
Group II
Prefoldins (PFD)
• Universally present in Eucarya and Archaea, with similar structures, but are
absent in bacteria
• Classified as a heterohexameric molecular chaperone 
• PFDs acts as a co-chaperone and facilitates the supply of unfolded or partially
folded substrates to class II chaperonins.
• Archaeal prefoldin recognises a wide range of unfolded substrates, whereas
eukaryotic prefoldin is highly specific.
• In Archaea Prefoldins function as “holdases” to capture and stabilize non-
folded polypeptides and deliver them to other chaperonins.
• In Archaeal PFD complexes, coiled coils are aligned in a way that hydrphobic
residues produce a cavity responsible for substrate binding.
• Thermococcus kodakaraensis KOD1 has two prefoldin proteins
Archaeal Prefoldin (GimC) from Methanothermobacter thermautotrophicus

The globular body and coiled coils

extensions in the “jellyfish” model form an
adjustable cage that accommodates and
binds proteins by a clamp mechanism

PDB ID: 1FXK

Dimeric form of PFD Two identical α and four identical β subunits

β1 𝛼 β2

`β1 `𝛼 `β2

The structure and molecular surface of the prefoldin hexamer

The subunits are arranged by hydrophobic interactions 

Small Heat Shock Proteins (sHSPs)
• sHSP genes are present in all Archaea
• The sHSPs share amino acid sequence similarity with the central core of
vertebrate eye lens 𝛼 -crystallin proteins.
• sHSPs and 𝛼-crystallins act as holdase-type molecular chaperones
• Archaeal sHSPs can prevent denatured proteins from aggregating under
strong denaturing conditions, and in some cases, are able to refold denatured
proteins
• They can maintain solubility of nonnative proteins under physiological
conditions,
• Hyperthermophilic species growing optimally near 100°C have one shsp gene,
with the exception of Pyrobaculum aerophilum, which has two homologs
Group II Chaperonins in Archaea
• Archaeal chaperonins are composed of up to five sequence-related
subunits
• The subunit composition of the chaperonin complexes in several archaea
changes with growth temperature
• A cold-adaptation response in M. burtonii has also been observed and
chapronines are produced at extremely low temperatures
• The halophilic archaeon H. volcanii has three group II chaperonins genes,
cct1, cct2, and cct3, which are all expressed but to differing expression
levels
Group II Chaperonins in Archaea
• The Thermococcus KS-1, α and β -subunits coassemble to form double-ring
homooligomers (α -chaperonin and β-chaperonins, respectively)
• These proteins are able to capture denatured proteins and fold them in an
ATP-dependent manner.
Proposed Mechanism
Group I Chaperonins in Methanosarcina Species
• M. mazei and M. acetivorans have revealed that these species contain both
group I and II chaperonin genes
• In M. mazei, both chaperonin complexes are formed from chaperonin
oligomers that are expressed from genes that are moderately induced by
heat stress
• The coexistence of both groups of chaperonins in the same cytosol in the
Methanosarcina species provides a useful model system for studying the
differential substrate specificities of the group I and II chaperonins