ANAHEIM, Calif. -- One of life's simplest organisms -- a mud-dwelling photosynthetic bacterium -- is helping scientists unlock the complex structural makeup that occurs when proteins come together to perform important biological duties.
Such knowledge, says Klaus Schulten of the University of Illinois, can shed light on what happens when proteins aggregate (combine and arrange) at the right time and when they do it at the wrong time, as is the case in diseases of the central nervous system such as Alzheimer's disease and bovine spongiform encephalopathy (Mad Cow Disease).
Speaking at the annual meeting of the American Association for the Advancement of Science, Schulten told how his theoretical biophysics group at the U. of I. Beckman Institute for Advanced Science and Technology combined X-ray crystallography and computational modeling to identify the structure of a protein called the two light-harvesting complex in the purple bacteria Rhodobacter sphaeroides. The protein is an aggregate of eight independent but identical units that form a highly symmetrical ring. A similar protein forms a ring of 16 units and surrounds the bacterium's photosynthetic reaction center.
The whole ensemble contains hundreds of chlorophylls as well as carotenoids, both of which are light-absorbing compounds that serve to harvest sunlight and funnel its energy to the centrally located reaction center.
Schulten, who holds the U. of I. Swanlund Chair in Physics, his Beckman Institute colleagues and collaborators of the Max Planck Institute for Biochemistry in Frankfort, Germany, first published their three-dimensional rendering in the May 1996 issue of the journal Structure. Subsequent accomplishments, including the creation of a colorful physical model of the photosynthetic center, based on the computer model, have been published in physics and biological journals and in the Proceedings of the National Academy of Sciences.
Using his hand-held, color-coded model, Schulten described how the components fit inside the ring: 24 chlorophylls (which make plants green); eight carotenoids (which make tomatoes red); and eight independent peptide units. They all collect and arrange into a protein membrane and feed energy into the bacterium's metabolism.
Having an accurate model of the structure, Schulten said, "is like having the Rosetta stone [a tablet of inscriptions found in 1799 that led to the deciphering of ancient Egyptian writing]; it provides us with the key for answering questions about the underlying physical components that go into the assembly and function of not only purple bacteria but also that of the light-harvesting complexes of more complex plants."
"This is a great example of how you can apply physics conceptually to biology to solve molecular mysteries," he said. "With this model, I can show how nature has molded a certain class of proteins to turn them into an apparatus that is uniquely effective in absorbing photons from the sun, conserving that energy and transporting it to certain points where other proteins take over the energy and use it. It provides us with a good example of the specialties within living systems. There are parts that can self-organize into very complex structures, and that ability is very distinct in organic systems."
His model is based on one of life's smallest systems. Purple bacteria live in the mud below surface plants. They are scavengers, feeding on bits, or photons, of sunlight that are not claimed by the plants. In fact, Schulten said, they "feed" on only two types of photons -- one with a wavelength of 500 nanometers and another of 800 nm -- which are absorbed, respectively, by the bacterium's carotenoids and chlorophylls. The carotenoids also play bodyguard to the chlorophylls and protect them from oxygen.
"Usually when you model something in a computer, you are not sure that what you do is reality and not just virtual reality," Schulten said. "But by having sufficient biological data, you can know that you are modeling correctly. In our case, the data without modeling could not be interpreted, but with the modeling we could complete a clear and correct structure of the light-harvesting protein."
Schulten's model shows "the beautiful capability of life to organize itself into components and do it spontaneously without something from the outside being there to place all the pieces together."
"It just happens spontaneously," he said. "But on the other side of the coin, something that works beautifully also can go wrong, and when it does you can have a lot of damage.
"Such unwanted assembly of protein can occur when the various components are not in complete order. They will still aggregate and form maybe beautiful structures, but they can be very detrimental. We know some of the resulting diseases very well," Schulten said. "One of them is Alzheimer's, in which certain proteins form plaques in the brain. Another is Mad Cow Disease, where a protein aggregates at the wrong time and causes a chain reaction of other proteins joining the aggregate."
Schulten told scientists at the AAAS that his model protein shows how "nature uses some very irregular forms to create something beautiful." But, he said: "I'm not saying that with this model we can cure Alzheimer's. There are many steps in understanding various biological systems. This model shows the structure of a protein in one of the purest, simplest systems. It has much to teach us about adhesion forces that govern self-assembly and how certain drugs may be targeted to interfere when assembly begins to occur at the wrong time."
CONTACTS: Klaus Schulten will be at the Anaheim Hilton and Towers, 714-750-8000, from late Saturday (Jan. 23) to early Tuesday (Jan. 26). After the AAAS meeting, he can be reached at his U. of I. office, 217-244-1604. Jim Barlow, life sciences editor of the U. of I. News Bureau, can be reached at the Anaheim Marriott, 714-750-8000, through mid-day Monday (Jan. 25), or after the AAAS meeting at 217-333-5802.