Designer lipid-like peptides stabilize membrane proteins

Abstract:

Membrane proteins play vital roles in many key functions of cellular activities.  In order to study diverse membrane proteins, it is crucial to select the right surfactants to stabilize them for biochemical and structural analysis.  Despite much effort, progress has been slow to elucidate their structure and function.  One of the aspects is due to lack of suitable surfactants.  We developed a class of designer short and simple lipid-like peptides that can stabilize several different types of membrane proteins including a G-protein coupled receptor bovine rhodopsin, plant and bacterial photosystem I.  These lipid-like peptide surfactants consist of seven amino acids with a hydrophilic head, aspartic acid or lysine, and a hydrophobic tail with six consecutive alanines or valines.  These designer peptide surfactants are simple, versatile and affordable.  They represent a new class of surfactants for studies of diverse elusive membrane proteins. 

Speaker: SHUGUANG ZHANG

Affiliation: Center for Biomedical Engineering NE47-379, Center for Bits & Atoms
Massachusetts Institute of Technology

Host: Margarida Archer

Short CV:

Shuguang Zhang’s laboratory focuses on developing new classes of biological materials using natural amino acids through molecular self-assembly. He employs the ‘bottom-up’ approach to produce new materials, molecule by molecule for novel supramolecular architectures.  Such approach requires a deep understanding of individual molecular building blocks, their structures, assembling properties and dynamic behaviors.  Two key elements in molecular fabrication are chemical complementarity and structural compatibility, both of which confer the weak and noncovalent interactions that bind building blocks together during molecular self-assembly.  Significant advances have been achieved at the interface of biology, chemistry and materials science including: 1) the fabrication of nanofiber scaffolds for 3-D cell cultures, tissue repair and regenerative medicine, 2) the designer peptide surfactants for stabilizing and crystallizing membrane proteins 3) designer peptide ink for surface bio-printing.  Molecular fabrications of biological materials accelerate diverse scientific discoveries and technological innovations. 

A brief biosketch: Shuguang Zhang is at the Center for Biomedical Engineering and Center for Bits & Atoms, Massachusetts Institute of Technology. He received his B.S. from Sichuan University in China and Ph.D. in biochemistry & molecular biology from University of California at Santa Barbara.  He was an American Cancer Society Postdoctoral Fellow at MIT and was a Whitaker Foundation Investigator.  He is member of AAAS, American Society of Biochemistry & Molecular Biology, the Protein Society, New York Academy of Sciences, Sigma Xi.  He received an honorary professorship from Sichuan University. He is also an elected Chang Jiang distinguished scholar in China. He is a 2003 Fellow of Japan Society for Promotion of Science (JSPS fellow).  His work of designer peptide scaffold won 2004 R&D100 award.  His and his colleagues’ work of direct harvesting biosolar energy was selected to be the Top 100 Science Stories in 2004 by Discover Magazine and one of the 10 finalists of the 2005 Saatchi & Saatchi Award for World Changing Ideas.  He is one of the 2006 John Simon Guggenheim Fellows.  He is the recipient of 2006 Wilhelm Exner Medal of Austria. 

Selected Publications (from over 100):
Zhang, S., Holmes, T., Lockshin, C. & Rich, A. (1993), Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane.  Proc. Natl. Acad. Sci. 90, 3334-3338.
Vauthey, S. Santoso, S., Gong, H., Watson, N. & Zhang, S. (2002) Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles.  Proc. Natl. Acad. Sci. USA 99, 5355-5360.
Zhang, S. (2003) Fabrication of novel materials through molecular self-assembly.  Nature Biotechnology 21, 1171-1178.
Kiley, P. Zhao, X., Vaughn, M., Baldo, M. Bruce, B.D. & Zhang, S. (2005) Self-assembling peptide detergents stabilize isolated photosystem I on a dry surface for an extended time. Public Library of Science  Biology. 3, 1181-1186.
Yokoi, H., Kinoshita, T. & Zhang, S. (2005) Dynamic reassembly of peptide RADA16 nanofiber scaffold. Proc. Natl. Acad. Sci. 102, 8414-8419.
Yeh, J. I., Du, S., Tordajada, A., Paulo, J., Zhang, S. (2005) Peptergent: peptide detergents that improve stability and functionality of a membrane protein glycerol-3-phosphate dehydrogenase. Biochemistry 44, 16912-16919.
Yang, S. & Zhang, S. (2006) Self-assembling behavior of short lipid-like peptides. Supramolecular Chemistry 18, 389-396.
Zhao, X., Nagai, Y., Revees, P., Kiley, P., Khorana, H.G. & Zhang, S. (2006) Designer lipid-like peptides significantly stabilize G-protein coupled receptor bovine rhodopsin. Proc. Natl. Acad. Sci. USA 103, 17707-17712.
Gelain, F., Bottai, D., Vescovi, A & Zhang, S. (2006) Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem cell 3-dimensional cultures. PLoS ONE 1, e119, 1-11.
Nagai, A., Nagai, Y., Qu, H., & Zhang, S. (2007) Self-assembling behaviors of lipid-like peptides A6D and A6K. J. Nanoscience & Nanotechnology 7, 2246–2252.
Maguire, Y., Chuang, I. L. Zhang, S. & Gershenfeld, N. (2007) Ultra-small-sample molecular structure detection using microslot nuclear spin resonance Proc. Natl. Acad. Sci. USA 104, 9198-9203