Researchers discover a new protein fold with a transport tunnel
Biochemists from Bielefeld, Toronto, Boston, and Kiel publish study in ‘Nature’
The protein LIMP-2 is vital for both humans and animals. If it is absent – due, for example, to a hereditary disease – substances of an unknown nature, probably lipids, accumulate in the organism. Up to now, scientists were unsure what the protein looks like and how exactly it functions. Privatdozent [senior lecturer] Dr. Michael Schwake from the Faculty of Chemistry at Bielefeld University (Germany) is doing research on the protein – and thereby preparing the way for future therapies. Together with colleagues in Kiel, Toronto, and Boston, he has now discovered that the protein LIMP 2 possesses a novel protein fold together with a nanomicroscopically small transport tunnel. The researchers have published their findings on Sunday (27 October) in the globally renowned scientific journal ‘Nature’.
To study LIMP-2, Schwake’s colleagues from the Canadian University of Toronto have crystallized the protein. Then they can use X-ray diffraction analysis to ascertain its crystalline structure. ‘When analysing the images, we detected a protein fold that has not been described in any other protein up to now,’ says Schwake.
LIMP-2 is present in every cell of the human body. It is found mostly in the lysosomes of the cells where it ensures that a specific enzyme reaches them. Lysosomes are the ‘stomachs’ of the cells and they break down harmful and unusable substances. A specific enzyme called beta-glucocerebrosidase is responsible for breaking down lipids. If this enzyme is defect or does not reach the lysosomes, these lipids will accumulate. Biochemists suspect that this is what causes Gaucher’s disease that leads to an enlarged liver and spleen.
Schwake’s studies confirm how LIMP-2 transports this enzyme. The protein has a ‘head’ consisting of several helices on which the enzyme docks. ‘We also managed to show that the protein is equipped with a tunnel through which it transports substances through membranes,’ Schwake reports. The biochemists have determined that it is highly probable that this channel is used to transport lipids away from the lysosome. ‘We determined that by comparing the structure of LIMP-2 with that of related proteins,’ says Schwake. Two of these proteins are known to bind and transport lipids. The comparison suggests that LIMP-2 must possess the same ability.
Since February 2013, PD Dr. Michael Schwake has been running a research team in the Biochemistry III Research Group at Bielefeld University’s Faculty of Chemistry headed by Professor Dr. Gabriele Fischer von Mollard. Before this, he was a researcher at the Institute of Biochemistry at Kiel University and at Stanford University (California). Schwake took his doctorate in 2001 at the Center for Molecular Neurobiology Hamburg and his post-doctoral habilitation in 2007 at Kiel University. For the study on LIMP-2, he worked with Professor Dr. Paul Saftig from the Institute of Biochemistry at Kiel University. He also cooperated with researchers at the Dana-Farber Cancer Institute in Boston (USA), the University of Toronto (Canada), the Li Ka Shing Knowledge Institute, and the SickKids Research Institute, both in Toronto.
Dante Neculai, Michael Schwake, Mani Ravichandran, Friederike Zunke, Richard Collins, Judith Peters, Mirela Neculai, Jonathan Plumb, Peter Loppnau, Juan Carlos Pizarro, Alma Seitova, William S. Trimble, Paul Saftig, Sergio Grinstein, Sirano Dhe-Paganon: Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36, Nature, http://dx.doi.org/ 10.1038/nature12684, published online on 27 October 2013.
PD Dr. Michael Schwake, Bielefeld University
Faculty of Chemistry
Telephone: +49 521 106-2091