In-cell imaging reveals bacterial protein transport-and-folding complex

Overview

Updated 2 hours ago

For forty years, the bacterial protein transport channel — the Sec translocon — was studied as an isolated molecule, purified out of cells and pinned in crystals. A new study watched the whole machine work inside a living bacterium and found it hitched to a dome-shaped folding chamber nobody had seen before.

The images, published September 25 in Cell, are the first sub-nanometer maps of the complete Sec machinery in its native membrane, taken in the near-minimal bacterium Mycoplasma pneumoniae. They show the ribosome passing a newborn protein straight to the channel, and three previously unknown proteins folding it into shape on the other side.

Why it matters

Seeing the full bacterial protein transport machine at work in a cell could sharpen antibiotic targets and improve engineered protein secretion.

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Key Indicators

New dome proteins found

Three uncharacterized Mdps form the extracellular folding chamber.

1.8%

Ribosome-dome complexes in untreated cells

Low baseline coupling between translation and translocation.

8-16%

Ribosome-dome complexes after translation halt

Enrichment when protein synthesis is stopped with antibiotics.

Sub-nm

Resolution of in-cell maps

First sub-nanometer views of the complete Sec machinery in cells.

Voices

Curated perspectives — historical figures and your fellow readers.

Ever wondered what historical figures would say about today's headlines?

People Involved

Julia Mahamid

Structural biologist, group leader at EMBL Heidelberg, senior author of the study

Group leader, EMBL Heidelberg

Rasmus K. Jensen

First author of the study

Researcher at EMBL

Joseph C. Somody

Co-author of the study

Researcher at EMBL

Organizations Involved

European Molecular Biology Laboratory (EMBL)

Research institute

Host institution for the study's lead group

A European molecular biology research institute headquartered in Heidelberg, Germany.

Cell

Scientific journal

Publisher of the study

A leading peer-reviewed journal in the life sciences, published by Cell Press.

Timeline

April 2025 September 2026

2 events Latest: Yesterday

September 2026
Cell publishes the peer-reviewed study
Latest Publication

The paper appears online with sub-nanometer in-cell maps of the complete Sec translocation-folding complex.
Yesterday
April 2025
Preprint posted on bioRxiv
Research

The team reports the discovery of a translocation-folding complex in Mycoplasma pneumoniae before peer review.
April 25th, 2025

Scenarios

Dome-folding complex found in other bacteria

Likely Resolves by Q2 2028

Discussed by: The study authors, who note whether similar mechanisms exist in other organisms remains to be explored

Cryo-ET screens of other bacteria — model organisms like E. coli or pathogens — reveal homologous dome complexes coupled to the Sec translocon. A structure-first study using the same pipeline on a second species would settle it.

Dome components engineered to boost protein secretion

Possible Resolves by End of 2028

Discussed by: Structural biology and synthetic biology commentators covering the paper

Researchers graft the dome folding chamber onto engineered secretion systems to improve yields of recombinant proteins in bacterial production. The three Mdps and their foldase activity become a biotech tool.

SecA co-translational handoff confirmed in E. coli

Possible Resolves by Q2 2028

Discussed by: The paper's authors, citing growing E. coli evidence for SecA-mediated co-translational translocation

Follow-up experiments confirm the model in E. coli, showing ribosomes hand nascent peptides to SecA physically across a wider range of bacteria. The current maps are the first direct in-cell evidence for this handoff.

Historical Context

2 moments from history that rhyme with this story — and how they unfolded.

1999–2009

Ribosome crystal structures (2000s)

X-ray crystallography produced atomic models of the ribosome, the cell's protein-making machine, after decades of effort. The 2009 Nobel Prize in Chemistry went to Venki Ramakrishnan, Thomas Steitz, and Ada Yonath for the work.

Then

Structural biology gained its most detailed view of a core cellular machine.

Now

Ribosome structures became a foundation for antibiotics research and a template for studying other complexes.

Why this matters now

The same ambition — resolve a cellular machine at atomic clarity — is now achieved inside the cell with cryo-ET, without purifying the complex first.

early 2010s

Nuclear pore complex in-cell cryo-ET (2010s)

Martin Beck's group at EMBL used cryo-electron tomography to build integrative models of the nuclear pore complex, the gatekeeper between nucleus and cytoplasm, from images of intact cells rather than purified samples.

Then

It became a landmark proof that large complexes could be resolved in their native context.

Now

It helped establish cryo-ET as in-cell structural biology and trained the methods used today.

Why this matters now

Mahamid's group, working in the same EMBL setting, extends that approach to a completely new machine.