Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Proteins by Design: Penn Biochemists Create New Protein from Scratch

Approach could one day be used to make artificial blood
No doubt proteins are complex. Most are “large” and full of interdependent branches, pockets and bends in their final folded structure. This complexity frustrates biochemists and protein engineers seeking to understand protein structure and function in order to reproduce or create new uses for these natural molecules to fight diseases or for use in industry.

Using design and engineering principles learned from nature, a team of biochemists from the University of Pennsylvania School of Medicine have built – from scratch – a completely new type of protein. This protein can transport oxygen, akin to human neuroglobin, a molecule that carries oxygen in the brain and peripheral nervous system. Some day this approach could be used to make artificial blood for use on the battle field or by emergency-care professionals. Their findings appear in the most recent issue of Nature.

“This is quite a different way of making novel proteins than the rest of the world,” says senior author P. Leslie Dutton, PhD, Eldridge Reeves Johnson Professor of Biochemistry and Biophysics. “We’ve created an unusually simple and relatively small protein that has a function, which is to carry oxygen. No one else has ever done this before.”

“Our aim is to design new proteins from principles we discover studying natural proteins,” explains co-author Christopher C. Moser, PhD, Associate Director of the Johnson Foundation at Penn. “For example, we found that natural proteins are complex and fragile and when we make new proteins we want them to be simple and robust. That’s why we’re not re-engineering a natural protein, but making one from scratch.”

Currently, protein engineers take an existing biochemical scaffold from nature and tweak it a bit structurally to make it do something else. “This research demonstrates how we used a set of simple design principles, which challenge the kind of approaches that have been used to date in reproducing natural protein functions,” says Dutton.

The natural design of proteins ultimately lies in their underlying sequence of amino acids, organic compounds that link together to make proteins. In living organisms, this sequence is dictated by the genetic information carried in DNA within chromosomes. This information is then encoded in messenger RNA, which is transcribed from DNA in the nucleus of the cell. The sequence of amino acids for a particular protein is determined by the sequence of nucleotides in messenger RNA. It is the order of the amino acids and the chemical bonds between them that establish how a protein folds into its final shape.

To build their protein, the Penn team started with just three amino acids, which code for a helix-shaped column. From this, they assembled a four-column bundle with loop that resembles a simple candelabra. They added a heme, a chemical group that contains an iron atom, to bind oxygen molecules. They also added another amino acid called glutamate to add strain to the candelabra to help the columns open up to capture the oxygen. Since heme and oxygen degrade in water, the researchers also designed the exteriors of the columns to repel water to protect the oxygen payload inside.

Initially, the team used a synthesizer – a robot that chemically sticks amino acids together in a desired sequence – to make the helix-shaped columns. “We do the first reactions with the robot to figure out the sequence of amino acids that we want,” says Moser. When they are satisfied with the sequence, they use the bacterium E. coli as a biological host to make the full protein.

The team used chemical tests to confirm that their protein did indeed capture oxygen. When the oxygen did bind to the iron heme molecule in the artificial protein, the solution in which the reaction took place changed color from dark red to scarlet, a color signature almost identical to natural neuroglobin.

“This exercise is like making a bus,” says Dutton. “First you need an engine and we’ve produced an engine. Now we can add other things on to it. Using the bound oxygen to do chemistry will be like adding the wheels. Our approach to building a simple protein from scratch allows us to add on, without getting more and more complicated.”

In addition to Dutton and Moser, co-first authors J.L. Ross Anderson, PhD, a postdoc in the Dutton lab and Ronald L. Koder, PhD, a former postdoc in the Dutton lab now with the Department of Physics at the City College of New York; Lee A. Solomon, a PhD student in the Dutton lab, and Konda S. Reddy, PhD, were also authors on the paper.

This work was funded by the Department of Energy, the National Institutes of Health, and the National Science Foundation.

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

Karen Kreeger | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>