Press Release
How cells export and embed proteins in the membrane
EMBL scientists first to visualise crucial step
© Schaffitzel / EMBL
Grenoble, 12 December 2010 - Like an overprotective parent
on the first day of school, a targeting factor sometimes needs
a little push to let go of its cargo. Scientists at the European
Molecular Biology Laboratory (EMBL) in Grenoble, France,
have visualised one such hand-over. They were the first to
determine the structure of a ribosome-protein complex
involved in carrying nascent proteins out of the cell. Their work,
published today in Nature Structural and Molecular Biology,
could increase understanding of illnesses such as cystic fibrosis
and some forms of Parkinson’s disease, in which improper
protein targeting leads proteins to harmfully accumulate inside
cells.
In most organisms, proteins destined to cross or be embedded
in a membrane contain a polypeptide sequence that is
recognized during translation by a targeting factor known
as the signal recognition particle (SRP). SRP binds to the
ribosome synthesizing the polypeptide, and subsequently also
binds an SRP receptor, located next to the machinery that
transfers proteins across the membrane and out of the cell.
EMBL scientists have now generated the first-ever structural
image of this important step in the process.
“The SRP receptor acts as a switch between the cargo binding
and the release,” says Christiane Schaffitzel, who led the
research at EMBL, “Now we have seen for the first time how
the release can happen at a molecular level.”
Schaffitzel’s group is taking structural snapshots of entire
pathways by which proteins are synthesized and targeted
to their final positions. To capture this hand-over step, the
scientists had to overcome the fact that the link between SRP
and its receptor is usually transient, chemically unstable. They
engineered the SRP receptor so that it would bind more stably
to SRP, then introduced ribosomes and observed the resulting
complexes using cryo-electron microscopy (cryo-EM).
This cryo-electron microscopy image shows the 3D structure of the
ribosome (yellow/blue) bound to the signal recognition particle (SRP)
and the SRP receptor (both in red). Below it is an atomic model of SRP
(green-yellow/orange) and its receptor (pink).
Cryo-EM can be performed in roughly physiological
conditions, providing a picture that closely resembles what
happens in living cells. This picture can then be combined
with higher-resolution crystallography data and biochemical
studies – an exciting hybrid approach the EMBL scientists will
further exploit to follow protein targeting all the way from start
to finish.
A particular asset for success in this project was the close
collaboration with Guy Schoehn at the Institut de Biologie
Structurale (IBS). IBS and EMBL are part of the Partnership
for Structural Biology (PSB) in Grenoble, France.
Source Article
Estrozi, L.F., Boehringer, D., Shan, S., Ban, N., Schaffitzel, C.. Cryo-EM structure of the E. coli translating ribosome in complex with SRP
and its receptor. Nature Structural and Molecular Biology, Advance Online Publication 12 December 2010.
Contact:
Sonia Furtado, EMBL Press Officer, Heidelberg, Germany, Tel: +49 6221 387 8263, www.embl.org, [email protected]
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