Chaperoning Anfinsen: the steric foldases

  title={Chaperoning Anfinsen: the steric foldases},
  author={Kristof Pauwels and Inge Van Molle and Jan Tommassen and Patrick van Gelder},
  journal={Molecular Microbiology},
Some proteins are so much resistant to proteolysis and unfolding that they violate folding rules shared by the vast majority of proteins. These unusual proteins manage to fold into an active native conformation that is thermodynamically at best marginally, but often even less stable than the unfolded state. A huge energetic barrier traps these proteins kinetically in the folded state. The drawback of this situation is the need for a specialized chaperone that adds steric information to the… 

The Chaperonopathies: Diseases with Defective Molecular Chaperones

This book describes chaperones with demonstrated chaperoning roles and other molecules related to them evolutionarily and/or functionally and focuses on conditions with chaperone malfunction and associated pathologies.

Decoding the Folding of Burkholderia glumae Lipase: Folding Intermediates En Route to Kinetic Stability

It is demonstrated that the native lipase has a kinetically stable conformation and it is shown that a newly discovered molten globule-like conformation has distinct properties that clearly differ from those of the near-native intermediate state.

Structural biology of periplasmic chaperones.

The Membrane‐Integrated Steric Chaperone Lif Facilitates Active Site Opening of Pseudomonas aeruginosa Lipase A

It is speculated that further interactions of PaLipA with the Xcp secretion machinery and/or components of the extracellular matrix contribute to the remaining activity of secreted PaLips, according to the computational and in vitro biochemical results.

Modeling protein folding in vivo

Computational modeling of protein folding should deemphasize the notion of unassisted thermodynamically controlled folding, and should focus instead on the step-by-step reverse engineering of the folding process as it actually occurs in vivo.

Studies of protein folding pathways

Realization of the simulated “oscillatory hydrophobic driving force” that mimics the quality control system in the endoplasmic reticulum (ER) may be of enormous practical value for protein folding at high concentrations.

Conserved Prosegment Residues Stabilize a Late-Stage Folding Transition State of Pepsin Independently of Ground States

Results indicated that the prosegment, which is only 44 residues long, has evolved a high density of contacts that preferentially stabilize the folding transition state over the ground states, postulated that the poetrygment forms extensive non-native contacts during the process of catalyzing correct inter- and intra-domain contact during the final stages of folding.

Structural Basis for Action of the External Chaperone for a Propeptide-deficient Serine Protease from Aeromonas sobria*

It is revealed that operons encoding subtilases and their external chaperones are widely distributed among Gram-negative bacteria, suggesting that ASP and its homologs form a novel family of subtilase family having an external chapersone.



Energetic landscape of α-lytic protease optimizes longevity through kinetic stability

It is demonstrated that this of folding and unfolding pathways has removed constraints placed on the folding of thermodynamically stable proteins, and allowed the evolution of a native state having markedly reduced dynamic fluctuations, which has led to a significant extension of the functional lifetime of αLP by the optimal suppression of proteolytic sensitivity.

Protein memory through altered folding mediated by intramolecular chaperones

The results indicate that an identical polypeptide can fold into an altered conformation through a mutated intramolecular chaperone and maintains memory of the folding process, which may be important in investigations of protein folding.

Unfolded conformations of α-lytic protease are more stable than its native state

It is shown that both the I and fully unfolded states of αLP are lower in free energy than the native state, and Native αLP is thus metastable.

Role of the lipase-specific foldase of Burkholderia glumae as a steric chaperone.

Results demonstrate that the Lif functions in a way analogous to the propeptides of many bacterial proteases and indicate that the amino acid sequence of the lipase does not contain all the information required for the protein to adopt its three-dimensional structure.

Convergent evolution of clamp-like binding sites in diverse chaperones

Molecular chaperones have evolved diverse tertiary and quaternary structures to stabilize non-native polypeptides and facilitate their transition to the native state. Indeed, different families of

Structure of α-lytic protease complexed with its pro region

While the majority of proteins fold rapidly and spontaneously to their native states, the extracellular bacterial protease α-lytic protease (αLP) has a t1/2 for folding of ~2,000 years, corresponding

Pilus chaperones represent a new type of protein-folding catalyst

Periplasmic type 1 pilus chaperone FimC binds non-native pilus subunits and accelerates folding of the subunit FimG by 100-fold, and represents a previously unknown type of protein-folding catalyst and simultaneously acts as a kinetic trap preventing spontaneous subunit assembly in the periplasm.

Kinetic stability as a mechanism for protease longevity.

Kinetic stability as a means to longevity is likely to be a mechanism conserved among the majority of extracellular bacterial pro-proteases and may emerge as a general strategy for intracellular eukaryotic proteases subject to harsh conditions as well.