I will give a brief overview of the major techniques (particularly crystallography) used in structural biology. Two of my current research projects that are closely related to the mission of the Nanobiotechnology Center (NBTC) will be discussed in detail. (1) We are working with the Luo Lab to use a cell-free protein producing gel (P-gel) for crystallization and structure determination of CD31, an important but difficult-to-express protein. CD31 plays an important role in many signal transduction events reactions and may be responsible for several biological and pathophysiological functions such as thrombosis, and inflammation. Also, as a cell surface receptor, CD31 can regulate lymophocyte adhesion to endothelial cells by interplaying with its counter-receptor CD38, whose structure has recently been solved by our group. A soluble fragment of CD31 (~50 kDa) containing N-terminal immunoglobulin-like domains has been shown to be sufficient for binding to CD38. A specific aim of this project is to determine the crystal structures of this N-terminal fragment and then the full-length CD31. (2) It is extremely challenging to obtain protein microtubular structures through self-assembly as proteins are very complex and flexible. I will present a strategy showing how a specific protein self-assembles into a helical hexagonal nanoparticle and further assembles to highly ordered crystalline microtubules. The structure of the protein nanoparticle was determined by X-ray crystallography at 4.5 Å resolution. The nanoparticle consists of six protein dimers and has dimensions of 5.6 nm by 5.6 nm by 35.6 nm. Higher order aggregation of the nanoparticles involves the formation of a nanorod from seven nanoparticles, which is consistent with the scanning electron microscopic observation. The preferential assemblies of protein nanorods generate microrods which further develop into microtubules through a proposed aging process.

Dr. Quan Hao studied physics at the University of Science and Technology of China (USTC), graduating with BSc in 1984. In 1988, he obtained his PhD in Solid State Physics at the Institute of Physics, Chinese Academy of Sciences, with research on the development of direct methods for phasing protein structures and incommensurately modulated structures. A Royal Society Fellowship enabled him to pursue his first postdoctoral training in Michael Woolfson s Lab at the University of York, England, where he continued on developing direct methods for structure solution. His second postdoctoral position was in John Helliwell and Marjorie Harding s lab at Daresbury Laboratory, where he gained substantial experience in experimental aspects of X-ray crystallography. He joined the faculty of De Montfort University (UK) in 1994 to teach biophysics. The timely award of a New Investigator Award from the Biotechnology and Biological Sciences Research Council (BBSRC) allowed him to set up a research program in protein crystallography. Dr. Hao moved to Cornell University in 2001 to become associate director, and then director, of the Macromolecular Facility of Cornell High Energy Synchrotron Source (MacCHESS). He is also an adjunct associate professor of Applied Engineering Physics (AEP). Specific research themes in his group include signaling proteins, enzyme substrate structures and catalysis. One project, that has excited media interest, is the structure determination of a multi-functional enzyme, human CD38. Human CD38 is physiologically recruited for the synthesis of several calcium messengers. His lab also determined the complex structures of the enzyme with its substrates, and with products.