Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Bacterial Protein Maturation

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...

Structure of Porins

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...

Protein Folding Quality Check in the RER

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Real-world experience of semaglutide 2.4 mg in the US: a retrospective analysis of profiles, satisfaction, and treatment patterns in people with obesity and overweight.

Current medical research and opinion·2026

Same author

Cross-Platform Assessment of Sub-50 nm Nanopipette Emitters for Native Electrospray Ionization Mass Spectrometry.

bioRxiv : the preprint server for biology·2026

Same author

Author Correction: High-throughput discovery of fluoroprobes that recognize amyloid fibril polymorphs.

Nature chemistry·2026

Same author

Phosphorylation tunes strain-specific protein condensation during rotavirus replication organelle assembly.

The EMBO journal·2026

Same author

Nanopipettes Enable Native Mass Spectrometry Studies of the Intrinsically Disordered Protein α-Synuclein in Biochemical Buffers.

Analytical chemistry·2026

Same author

Unmasking Hidden Monoclonal Proteins: Leveraging the Lipemia Index.

The journal of applied laboratory medicine·2026

Search research articles

Related Experiment Video

Updated: Jul 12, 2026

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

BAM-BepA complexes in outer membrane protein quality control.

Katherine L Fenn¹, Victoria Higgins¹, Jonathan M Machin¹

¹Astbury Centre for Structural Molecular Biology and School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.

Nature Communications

|July 9, 2026

Summary

The β-barrel assembly machinery (BAM) complex interacts with the β-barrel assembly enhancing protease A (BepA) to degrade misfolded outer membrane proteins (OMPs). BepA

More Related Videos

The MultiBac Protein Complex Production Platform at the EMBL

The MultiBac Protein Complex Production Platform at the EMBL

Published on: July 11, 2013

Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis

Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis

Published on: May 23, 2021

Related Experiment Videos

Last Updated: Jul 12, 2026

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

The MultiBac Protein Complex Production Platform at the EMBL

The MultiBac Protein Complex Production Platform at the EMBL

Published on: July 11, 2013

Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis

Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis

Published on: May 23, 2021

Area of Science:

Microbiology
Structural Biology
Protein Biochemistry

Background:

The outer membrane (OM) barrier function of bacteria relies on correct folding of outer membrane proteins (OMPs) by the β-barrel assembly machinery (BAM).
The β-barrel assembly enhancing protease A (BepA) is involved in OMP quality control when biogenesis is disrupted, but its mechanism of action with BAM is unknown.

Purpose of the Study:

To elucidate the structural basis of BepA interaction with BAM and its role in the proteolytic degradation of misfolded OMPs.

Main Methods:

Cryo-electron microscopy (cryoEM) to determine the structures of BAM-bound BepA.
Analysis of BepA conformational changes and substrate recognition motifs.

Main Results:

BepA binding induces significant conformational changes in the BAM complex, positioning BepA's active site for proteolysis.
BepA's lid region inserts into the membrane, and its plug movement is triggered by OMP binding, not BAM interaction.
BepA preferentially recognizes Aromatic-X-Aromatic (Ar-X-Ar) motifs common in OMP sequences.

Conclusions:

BepA utilizes a unique mechanism involving conformational changes in BAM, membrane insertion, and specific OMP motif recognition for proteolytic degradation.
This study reveals the molecular details of BepA-mediated OMP quality control, highlighting the interplay between BAM, the membrane, and OMP substrates.