Navigation Links
Protein structure: Peering into the transit pore

The lipid-rich membranes of cells are largely impermeable to proteins, but evolution has provided a way through in the form of transmembrane tunnels. A new study shows in unmatched detail what happens as proteins pass through such a pore.

Every cell is surrounded by a surface membrane and contains internal compartments bounded by membranes. Almost one-third of all proteins synthesized in cells must pass through these membranes or be incorporated into them in order to fulfil their functions. However, the fat-rich nature of membranes makes it impossible for most proteins to percolate through them directly. Therefore, biological membranes contain so-called protein-conducting channels, molecular pores through which proteins can pass. "Structural investigations have already provided clues to how proteins are inserted into the membrane and then drawn through it like a length of thread to emerge on the other side," says Professor Roland Beckmann of the Gene Center of Ludwig-Maximilians-Universitaet (LMU) in Munich. "However, conclusive proof for these mechanisms has been lacking until now."

Protein-conducting channels are known to be shaped like an hour-glass, consisting of two cones connected by a narrow central constriction. In the inactive form, the constriction is blocked by a plug that protrudes from the side-wall. Presumably, if a protein is to cross the membrane, the channel must be opened to provide a continuous aqueous environment for its passage. If, on the other hand, a protein is to be inserted within the membrane itself, it must emerge from a lateral opening within the tunnel.

Imaging the crucial transition

"Up until now, it had not been possible to characterize these structural transitions with the required spatial and temporal resolution," Beckmann says. Now he and his colleagues have, for the first time, succeeded in isolating transitional forms of the active channel, and elucidating their three-dimensional structures with the help of cryo-electron microscopy at the unprecedented resolution of less than 1 nanometer. "This allowed us to determine the spatial conformations of the individual protein strands that make up the channel and to analyze how the channel behaves during its functional cycle," he explains.

Indeed, the researchers were even able to capture a snapshot of the complex at the moment when a protein leaves the channel to be incorporated into the cell membrane. "It turns out that there actually is a side-door within the channel, which opens to allow the protein to diffuse into the membrane," Beckmann says. Interestingly, as the lateral gate opens and the protein exits the channel into the membrane, the plug moves into the central constriction, blocking access to the outside and preventing diffusion of ions through the now empty channel. Surprisingly, proteins destined to cross the membrane do so without altering the position of the plug very much. Instead, an adjacent strand shifts slightly outward, widening the constriction sufficiently to let the protein through the length of the tunnel.

Beckmann and his team now hope to be able to increase the resolution of their snapshots still further. "Our goal is to achieve a resolution of less than 0.4 nm, in order to discern the interactions in molecular detail and understand the dynamic changes that take place in the structure of the channel," he says. In addition, the scientists want to image other membrane protein complexes such as visual pigments and analyze how a single chain of amino acids can function as a dynamically active membrane receptor.


Contact: Luise Dirscherl
Ludwig-Maximilians-Universitt Mnchen

Related biology news :

1. Protein synthesis and chance
2. Designer proteins provide new information about the bodys signal processes
3. The Protein Society announces the selection of 2 Protein Science Best Paper speakers
4. Researchers tune in to protein pairs
5. FASEB announces 2014 Science Research Conference: Protein Folding in the Cell
6. FASEB announces 2014 SRC: Protein Phosphorylation, Cellular Plasticity & Signaling Rewiring
7. FASEB announces 2014 SRC: Protein Interactions, Structures, Technologies & Networks
8. High-protein diets, like the Dukan diet, increase the risk of developing kidney disease
9. Overexpression of splicing protein in skin repair causes early changes seen in skin cancer
10. Next-gen reappraisal of interactions within a cancer-associated protein complex
11. Researchers pursuing arthritis protein
Post Your Comments:
(Date:10/29/2015)... Calif. , Oct. 29, 2015  The J. ... new report titled, "DNA Synthesis and Biosecurity: Lessons Learned ... the Department of Health and Human Services guidance for ... in 2010. --> ... it also has the potential to pose unique biosecurity ...
(Date:10/29/2015)... NXTD ) ("NXT-ID" or ... the growing mobile commerce market and creator of ... leading marketplace to discover and buy innovative technology ... on StackSocial for this holiday season.   ... a biometric authentication company focused on the growing ...
(Date:10/27/2015)... SAN JOSE, Calif. , Oct. 27, 2015 /PRNewswire/ ... human interface solutions, today announced that Google has adopted ... family of touch controller solutions to power its newest ... Nexus 6P by Huawei. --> ... ecosystem partners like Google to provide strategic collaboration in ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... 2015 , ... InSphero AG, the leading supplier of easy-to-use solutions for production, ... to serve as Chief Operating Officer. , Having joined InSphero in November ... and was promoted to Head of InSphero Diagnostics in 2014. There she has ...
(Date:11/24/2015)... HemoShear Therapeutics, LLC, a privately held ... disorders, announced today the appointment of H. ... (BOD). Mr. Watkins is the former president and ... and also served as the chairman of the ... Chairman and CEO of HemoShear Therapeutics. "The combination ...
(Date:11/24/2015)... Nov. 24, 2015 According to two new studies, ... This is something that many doctors, scientists, and public health ... remains: with fewer PSA tests being done, will there be ... Dr. David Samadi, "Despite the efforts made in ... the second leading cancer cause of death in men, killing ...
(Date:11/23/2015)... ... November 23, 2015 , ... Shimadzu Corporation ... its Nexera UC Unified Chromatography system. The award from R&D magazine recognizes Shimadzu’s ... of the year in the analytical and testing category. R&D Magazine chose the ...
Breaking Biology Technology: