Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure reveals details of cell’s cargo-carriers

19.09.2002


Using x-ray crystallography, researchers have produced the first images of a large molecular complex that helps shape and load the small, bubble-like vesicles that transport newly formed proteins in the cell. Understanding vesicle "budding" is one of the prerequisites for learning how proteins and other molecules are routed to their correct destinations in the cell.



In an article published in the September 19, 2002, issue of the journal Nature, Howard Hughes Medical Institute (HHMI) investigator Jonathan Goldberg, Xiping Bi and Richard Corpina at Memorial Sloan-Kettering Cancer Center unveil the intricate architecture of the "pre-budding complex," which is a set of proteins that participates in the formation of vesicles on the cell’s endoplasmic reticulum (ER). The pre-budding complex is the triggering component of a protein coat called COPII that grabs a section of the ER membrane, pinches it off to form the vesicle and packages the protein cargo to be transported.

"The structure developed by Bi, Corpina and Goldberg makes an important contribution to the understanding of vesicle formation -- a process central to the transport of newly formed proteins," said HHMI investigator Randy Schekman, a pioneer in vesicle studies at the University of California, Berkeley. "It illuminates in detail the mechanism by which the core complex of the COPII protein coat assembles on the ER membrane to initiate the process of membrane cargo capture and vesicle budding." Schekman and James Rothman of Memorial Sloan-Kettering Cancer Center, working independently, have identified many of the fundamental details of protein transport and secretion.


Goldberg said the entire pre-budding complex was considered an important structure to solve because of COPII’s role in protein transport. "What makes the COPII coat unique is that encoded in its proteins is much of the information that tells it to go to the endoplasmic reticulum and which cargo to take up from the ER," said Goldberg. "Also, COPII selects the appropriate fusion machinery, to ensure that the vesicle fuses with its correct target, a structure called the Golgi complex."

In order to understand the process of vesicle formation and transport in molecular terms, one must begin with the initiating event -- with the multi-component pre-budding complex, Goldberg said. "We had to get a clear structural picture of the intact particle so that we can understand the first event in budding, which begins the process of selecting the protein cargo," he said.

Bi, Corpina and Goldberg produced crystals of the entire complex and analyzed the structures of the proteins using x-ray crystallography. Their studies revealed how each of the components of the complex works: A component called Sar1 launches the budding process by anchoring itself to the ER membrane. Sar1 accomplishes this feat by changing its shape through a chemical reaction called GTP binding.

This shape change also enables Sar1-GTP to recruit a second component called Sec23/24, which attaches to form the pre-budding complex, Sec23/24-Sar1. The structure produced by Goldberg and his colleagues reveals how the change in Sar1’s shape enables Sec23/24 to recognize Sar1 and attach to it.

The scientists discovered that the pre-budding complex has a concave surface that hugs the ER membrane, conforming to the spherical shape that the vesicle will ultimately assume. According to Schekman, "the structure reveals the mechanism by which the complex anchors to the ER membrane and how its curvature might impart curvature to the membrane; and in doing so initiate the shape change that accompanies vesicle budding."

Goldberg’s group also identified the part of the complex that faces away from the ER membrane, which includes components that attract another molecule that knits together, or "polymerizes," the coat, pinching off the vesicle from the ER membrane like a mold. The new structure hints at how the coat disassembles itself by, in effect, "breaking the mold" around the vesicle, and freeing it to carry its protein cargo away to be released at the right place in the cell.

Now that they have solved the structure of the pre-budding complex, Goldberg and his colleagues can begin to explore another central question -- how do the vesicles "know" which proteins to take on as cargo?

"We suspect -- and it is a model that Randy Schekman put forward several years ago -- that the COPII coat is selecting many of the proteins directly," said Goldberg. "As we explore the coat structure further, I suspect we will see lots of binding-site ’ crevices’ that specific cargo can plug into and thereby enter the vesicle. So, our next task is to look for those crevices."

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org/

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

More genes are active in high-performance maize

19.01.2018 | Life Sciences

How plants see light

19.01.2018 | Life Sciences

Artificial agent designs quantum experiments

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>