Chaperones - Latest research and news (2025)

Structural recognition and stabilization of tyrosine hydroxylase by the J-domain protein DNAJC12

DNAJC12 variants cause parkinsonism. Here, the authors show that DNAJC12 stabilizes tyrosine hydroxylase, a crucial enzyme in dopamine synthesis, and identify key structural motifs for this interaction, explaining the pathogenesis of truncated variants.

• Mary Dayne S. Tai
• Lissette Ochoa
• Aurora Martinez

Mechanism of ASF1 engagement by CDAN1

CDAN1 is an essential protein with unclear function that binds the histone chaperone ASF1. Here, the authors reveal that CDAN1 sequesters multiple copies of ASF1 by engaging all binding sites known to facilitate histone chaperoning.

• Samantha F. Sedor
• Sichen Shao

Native Fold Delay and its implications for co-translational chaperone binding and protein aggregation

During vectorial protein translation, native interactions are temporarily unsatisfied. Here, authors introduce “Native Fold Delay”, integrating protein topology with translation kinetics to quantify the resulting delays in co-translational folding which may result in protein aggregation.

• Ramon Duran-Romaña
• Bert Houben
• Joost Schymkowitz

Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes

Saturated fatty acid (SFA) and unsaturated fatty acid (UFA) have distinct impacts on health. Here the authors demonstrate that the secretion of UFA esters fromthe liver requires PDI-MTP, while secretion of SFA esters could bePDI-MTP-independent.

• Fengwu Chen
• Aizhen Yang
• Yi Wu

A ribosome-associating chaperone mediates GTP-driven vectorial folding of nascent eEF1A

Folding of abundant, complex proteins can begin during their synthesis. Here, Sabbarini et al. show that the conserved protein Ypl225w (Chp1) functions as a co-translational chaperone for eEF1A and identify a role for NAC in the process as a recruitment factor.

• Ibrahim M. Sabbarini
• Dvir Reif
• Vladimir Denic

Identification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development

• Katharina Weinhäupl
• Louis Meuret
• Hugo Fraga

Multidomain interactions and ring opening of the p97 ATPase by the UBXD1 adapter

The human ATPase p97 (also known as VCP) unfolds protein substrates by translocating them through its central channel. This process is highly regulated by numerous adapter proteins. Structures of p97 in complex with the unusual adapter UBXD1 reveal how this protein coordinates p97 hexamer remodeling and ring opening by expansive interactions across multiple p97 protomers.

Saving ribosomal proteins for later

Disruption of ribosome assembly results in the accumulation of aggregation-prone ‘orphaned’ ribosomal proteins that are toxic to cells if left unchecked. A study finds that cells store such ribosomal proteins during heat shock to enable a quick recovery of ribosome assembly after the removal of this stress.

• Joshua J. Black
• Rachel Green

Epichaperomics reveals dysfunctional chaperone protein networks

Molecular chaperones establish essential protein-protein interaction networks. Modified versions of these assemblies are generally enriched in certain maladies. A study published in Nature Communications used epichaperomics to identify unique changes occurring in chaperone-formed protein networks during mitosis in cancer cells.

• Mark R. Woodford
• Dimitra Bourboulia
• Mehdi Mollapour

Polymeric protagonists for biological processes

Complexity is a hallmark of biological systems, but scientific experiments are typically conducted in simplified conditions. Now, diverse polymers that mimic the local environments of complex biological mixtures have been shown to improve protein folding, stability and function.

• Alana P. Gudinas
• Danielle J. Mai

Searching for a chaperone

• Kate de Mattos-Shipley

Chaperoning the nuclear envelope

FG-nucleoporins of the nuclear pore complexes form a permeability barrier between the nucleus and the cytosol. FG-nucleoporins contain disordered regions and are prone to aggregation. Two studies identify the chaperone DNAJB6 as a key factor that prevents aggregation of FG-nucleoporins and assists in the biogenesis of nuclear pore complexes.

• Janine Kirstein