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 Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>