Featured Research

from universities, journals, and other organizations

Folding funnels key to biomimicry

Date:
October 31, 2012
Source:
DOE/Lawrence Berkeley National Laboratory
Summary:
Researchers have shown that a concept widely accepted as describing the folding of a single individual protein is also applicable to the self-assembly of multiple proteins. Their findings provide important guidelines for future biomimicry efforts, particularly for device fabrication and nanoscale synthesis.

AFM micrograph of 2D S-layers assembled on mica shows two different pathways to crystalization, one in which the domans are 2-3 nanometers taller (white circles). Height differences, measured along the dotted black line, were the result of kinetic trapping.
Credit: Image from Molecular Foundry

Proteins are able to self-assemble into a wide range of highly ordered structures that feature a diverse array of properties. Through biomimicry -- technological innovation inspired by nature -- humans hope to emulate proteins and produce our own version of self-assembling molecules. A key to accomplishing this is understanding how protein-folding -- a process critical to the form and function of a protein -- is extended from individual proteins to complex assemblies.

Researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) have now shown that a concept widely accepted as describing the folding of a single individual protein is also applicable to the self-assembly of multiple proteins. Their findings provide important guidelines for future biomimicry efforts, particularly for device fabrication and nanoscale synthesis.

"We've made the first direct observations that the concept of a folding funnel with kinetic energy traps for individual proteins can be equally applied to the assembly of ordered protein structures," says Jim DeYoreo, a scientist with the Molecular Foundry, a DOE nanoscience center at Berkeley Lab, who led this research along with Berkeley Lab chemist Carolyn Bertozzi. "Our results tell us that efforts to discover and codify the design rules for the self-assembly of complex molecular systems will have to take into account the impact of kinetic traps associated with conformational transformations."

DeYoreo and Bertozzi are the corresponding authors of a paper published by the Proceedings of the National Academy of Sciences (PNAS) that reported this research.

Proteins are essentially biomolecular nanomachines capable of performing numerous tasks because of their ability to fold themselves into a multitude of shapes and forms. When individual proteins self-assemble into ordered structures the resulting ensemble often adopts conformations that are quite distinct from those of the individual components.

"For example, collagen matrices, which constitute the organic scaffolds of bones and teeth, are constructed from triple helices of individual collagen monomers," DeYoreo says. "These helices will further assemble into highly organized twisted fibrils that exhibit a pseudohexagonal symmetry."

The folding funnel concept explains individual protein folding on the basis of conformational changes to reach a state of minimal free energy. An unfolded protein starts out in a state of high free energy that makes its conformation unstable. Initially, there are a number of possible three-dimensional conformations that would reduce this free energy. However, as the protein starts to fold, the free energy begins to drop and the number of possible conformations begins to decrease like the shrinking width of a funnel. The bottom of the funnel is reached when free energy is minimized and there is only one available conformation. As the free energy drops, however, there may be kinetic traps along the way that can stop the folding process and hold the protein in partially folded conformations, known as molten globules and folding intermediates, for extended periods of time. Eventually these trapped conformational states will be transformed into a stable conformation but the shape and form of that final conformation is influenced by the kinetic traps.

"In a protein folding funnel, the funnel walls are presumed not to be smooth and the resulting bumps and valleys define kinetic traps," DeYoreo says. "This physical picture of folding has been explored in some detail at the single molecule level, but has not been considered for protein self-assembly into extended architectures even though conformational transformations are part and parcel of the self-assembly process."

DeYoreo, Bertozzi and their colleagues took steps to correct this knowledge deficit by studying the surface-layer (S-layer) proteins that self-assemble into a crystalline membrane around the single cells of bacteria and Archaea. This outer membrane serves as the first point of contact between the microbe and its environment and is key to the microbe's ability to survive. Using in situ Atomic Force Microscopy (AFM), the researchers imaged in real time and at the molecular level kinetic trapping during the 2D self-assembly of S-layer protein structures on mica surfaces.

"We observed that self-assembly of S-layer proteins tracks along two different pathways, one leading directly to the low-energy final, ordered state, and the other leading to a kinetic trap occupied by a long-lived transient state that is more disordered," DeYoreo says. "Although either state is easily accessible during crystal nucleation, if the system falls into the high-energy state, escape to the final, low-energy state is strongly impeded at room temperature. This demonstrates the importance of kinetic traps in determining the pathway of S-layer crystallization and suggests that the concept of folding funnels is equally valid for self-assembly of extended protein structures."

This research was supported by the DOE Office of Science.


Story Source:

The above story is based on materials provided by DOE/Lawrence Berkeley National Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. S.-H. Shin, S. Chung, B. Sanii, L. R. Comolli, C. R. Bertozzi, J. J. De Yoreo. Direct observation of kinetic traps associated with structural transformations leading to multiple pathways of S-layer assembly. Proceedings of the National Academy of Sciences, 2012; 109 (32): 12968 DOI: 10.1073/pnas.1201504109

Cite This Page:

DOE/Lawrence Berkeley National Laboratory. "Folding funnels key to biomimicry." ScienceDaily. ScienceDaily, 31 October 2012. <www.sciencedaily.com/releases/2012/10/121031161042.htm>.
DOE/Lawrence Berkeley National Laboratory. (2012, October 31). Folding funnels key to biomimicry. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2012/10/121031161042.htm
DOE/Lawrence Berkeley National Laboratory. "Folding funnels key to biomimicry." ScienceDaily. www.sciencedaily.com/releases/2012/10/121031161042.htm (accessed July 25, 2014).

Share This




More Plants & Animals News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Boy Attacked by Shark in Florida

Boy Attacked by Shark in Florida

Reuters - US Online Video (July 24, 2014) An 8-year-old boy is bitten in the leg by a shark while vacationing at a Florida beach. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Goma Cheese Brings Whiff of New Hope to DRC

Goma Cheese Brings Whiff of New Hope to DRC

Reuters - Business Video Online (July 24, 2014) The eastern region of the Democratic Republic of Congo, mainly known for conflict and instability, is an unlikely place for the production of fine cheese. But a farm in the village of Masisi, in North Kivu is slowly transforming perceptions of the area. Known simply as Goma cheese, the Congolese version of Dutch gouda has gained popularity through out the region. Ciara Sutton reports. Video provided by Reuters
Powered by NewsLook.com
Dogs Appear To Become Jealous Of Owners' Attention

Dogs Appear To Become Jealous Of Owners' Attention

Newsy (July 23, 2014) A U.C. San Diego researcher says jealousy isn't just a human trait, and dogs aren't the best at sharing the attention of humans with other dogs. Video provided by Newsy
Powered by NewsLook.com
Professor Creates Site Revealing Where People's Cats Live

Professor Creates Site Revealing Where People's Cats Live

Newsy (July 23, 2014) ​It's called I Know Where Your Cat Lives, and you can keep hitting the "Random Cat" button to find more real cats all over the world. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins