Study shows short peptides can self-assemble into catalysts

Mar 17, 2014 by Bob Yirka report
Overview of concept and design. a, Structure of human carbonic anhydrase showing a typical metal-binding motif. b, Model for one of the designed peptides (11, Ac-IHIHIQI-CONH2) in the extended b-strand configuration showing positions of the residues in the sequence. c–e, Computationally derived model of fibrils formed by 11, showing overall fold (c), packing of the hydrophobic core (d) and zinc primary coordination sphere (e). Credit: Nature Chemistry (2014) doi:10.1038/nchem.1894

( —A team of researchers with members from Syracuse University and the University of California, has found that naturally forming peptides can self-assemble into catalysts. In their paper published in the journal Nature Chemistry, the team describes how they designed seven peptides, allowed the resulting molecules to self-assemble into amyloids and then noted how many of them could catalyze the hydrolysis of esters.

Scientists have long wondered how enzymes could have possibly come to exist in the that existed on Earth so long ago, leading to life as we know it. Enzymes, necessary for , are made of large complicated (folded into three dimensions) proteins, with long chains of amino acids. That they could self-assemble into the structures we see today seems nearly impossible, even given millions of years (leading to the belief by some of the idea of ). Yet, life clearly exists, which means something, if not the hand of God, had to have happened to get them started. In this new effort, the researchers wondered if perhaps a simpler structure might have come to exist first, which then might have served as a step towards the development of enzymes. In this case, they wondered if such structures might have been amyloid plaques—the same type of molecule clusters found in the brains of Alzheimer's patients. Amyloids are much simpler than enzymes—so much so that most would believe they could come to exist without a guiding hand from an ethereal source.

To learn more, the team created seven modest peptides, each of which were constructed from just seven —putting them together in a dish, with a dash of zinc iron to help move things along, allowed the peptides to self-form into different sheet-like fibril amyloids. During testing, four of the amyloids the team created were found to be able to catalyze the hydrolysis of esters.

The results of the team's experiments suggest that enzymes didn't necessarily have to spring forth fully formed from the primordial soup for life to begin, perhaps amyloids came first, serving as an intermediary, or a sort of blueprint—over millions of years the could have given way to the much more complicated enzymes, leading eventually to living organisms.

Explore further: Alzheimer substance may be the nanomaterial of tomorrow

More information: Short peptides self-assemble to produce catalytic amyloids, Nature Chemistry (2014) DOI: 10.1038/nchem.1894

Enzymes fold into unique three-dimensional structures, which underlie their remarkable catalytic properties. The requirement to adopt a stable, folded conformation is likely to contribute to their relatively large size (>10,000 Da). However, much shorter peptides can achieve well-defined conformations through the formation of amyloid fibrils. To test whether short amyloid-forming peptides might in fact be capable of enzyme-like catalysis, we designed a series of seven-residue peptides that act as Zn2+-dependent esterases. Zn2+ helps stabilize the fibril formation, while also acting as a cofactor to catalyse acyl ester hydrolysis. These results indicate that prion-like fibrils are able to not only catalyse their own formation, but they can also catalyse chemical reactions. Thus, they might have served as intermediates in the evolution of modern-day enzymes. These results also have implications for the design of self-assembling nanostructured catalysts including ones containing a variety of biological and non-biological metal ions.

add to favorites email to friend print save as pdf

Related Stories

Understanding abnormal proteins in degenerative diseases

Apr 22, 2013

Amyloids, or fibrous aggregates of abnormally folded proteins, are a common feature in degenerative diseases such as Alzheimer's, diabetes and cancer. Amyloids occur naturally in the body, but despite decades ...

New findings challenge assumptions about origins of life

Sep 13, 2013

Before there was life on Earth, there were molecules. A primordial soup. At some point a few specialized molecules began replicating. This self-replication, scientists agree, kick-started a biochemical process that would ...

Alzheimer substance may be the nanomaterial of tomorrow

Dec 16, 2013

Amyloid protein causes diseases like Alzheimer's, Parkinson's and Creutzfeldt-Jakob disease. But amyloid also carries unique characteristics that may lead to the development of new composite materials for ...

Researchers hone in on Alzheimer's disease

Feb 18, 2014

Researchers studying peptides using the Gordon supercomputer at the San Diego Supercomputer Center (SDSC) at the University of California, San Diego (UCSD) have found new ways to elucidate the creation of the ...

Recommended for you

Chemical biologists find new halogenation enzyme

8 hours ago

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

14 hours ago

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

14 hours ago

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

Decoding 'sweet codes' that determine protein fates

16 hours ago

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of ...

Conjecture on the lateral growth of Type I collagen fibrils

Sep 12, 2014

Whatever the origin and condition of extraction of type I collagen fibrils, in vitro as well as in vivo, the radii of their circular circular cross sections stay distributed in a range going from 50 to 100 nm for the most ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Mar 18, 2014
"Amyloids are much simpler than enzymes—so much so that most would believe they could come to exist without a guiding hand from an ethereal source".
What kind of comment is this? Does it really have its place in a scientific article about peptides?