Biophysical Society Newsletter | December 2017

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BIOPHYSICAL SOCIETY NEWSLETTER

2017

DECEMBER

attend scientific conferences, which opened my eyes to the world,” he says. For his postdoc, he joined Werner Kühlbrandt ’s group at European Molecular Biology Labora- tory (EMBL), Heidelberg. There he worked on determining the structure of the plant light-harvest chlorophyll-protein complex II (LHC-II), using a type of cryo-electron microscopy — electron crystallography — from two-dimensional crys- tals. “This was around the time when Richard Henderson at the MRC Laboratory of Molecular Biology was about to finish the bacteriorhodopsin structure, which he published at 3.5 Å resolution in 1990. We were following in Richard’s and Nigel Unwin ’s footsteps,” he says. “With help from Yoshinori Fujiyoshi , then at the Protein Engineer- ing Research Institute in Osaka, in 1994 Werner and I were able to solve the LHC-II structure at 3.4 Å resolution. The resolution was high enough to allow us to trace the amino acid side chains and to visualize a dozen chlorophyll and two lutein molecules, which told us a lot about how plants harvest sunlight for photosynthesis.” Reinhart Reithmeier from the University of To- ronto introduced Wang to membrane transport- ers. “While I was still working on the structure of LHC-II in Werner’s lab at EMBL, Reinhart came to Heidelberg to visit. Over a beer, Reinhart convinced me that membrane transporters, par- ticularly his favorite, the anion exchanger 1 (AE1), would be worthy targets for structure determina- tion,” he shares. “After returning to Toronto, he started shipping purified AE1 samples to Heidel- berg. I did manage to get a low-resolution EM structure of AE1. When I left Werner’s group to start my own lab at NYU, he generously let me take the project with me. Since then, my lab has been focusing on membrane transporters.” Over the years, members of Wang’s lab have crystallized and solved the atomic structures of a number of proteins. “One of them is the glycerol-3-phosphate transporter structure that we solved in 2003 — one of the first two structures determined from the major facilitator superfam- ily (MFS) — the other one by the lab of Ron Kaback at UCLA. The MFS family is the largest secondary transporter family; the human genome

contains over 100 members and E. coli more than 70. These members transport anything small and hydrophilic across the cell membrane. Our crystal structure helped a lot of investigators with work on their favorite MFS proteins,” he explains. Another was the bacterial dicarboxylate transporter VcIN- DY, the human homolog of which is involved in epilepsy in newborns and obesity in adults. “With such structural information in hand, we often collaborate with friends who use complementary techniques to look at the system from multiple angles, which is great fun,” Wang says. Joanne Lemieux , University of Alberta, was Wang’s first research technician, who helped him set up his lab at NYU in 1995. After working together for two years, he supported her decision to pursue a PhD, and she became his first PhD student. “Da-Neng’s most memorable quality is his car- ing attitude for his team of people in the lab. He fostered teamwork and collaborative learning,” she shares. He also taught Lemieux a valuable lesson that has helped her throughout her career. “As a junior scientist I was often caught up in the details of the methodologies, but his most sage advice was to focus on the bigger picture,” she says. “He en- couraged me to ask what contribution my research was making to the field.” Going forward, Wang hopes that his lab will help find ways to apply single-particle cryo-EM struc- ture determination to small proteins. In addition, he and several labs from different areas of biophys- ics have come together to explore how membrane transporters work in real time — to push their understanding to a level similar to that of ion channels. Outside of the lab, Wang enjoys spending time with his family and participating in less-than- adventurous hobbies. “I wish I could say that I climbed Everest or have run a marathon, but my life is a lot less exciting,” he jokes. “I do enjoy travel and seeing different parts of the world. On weekends, I hike a bit in New Jersey or upstate New York. During my daily commute to work, I read history books and biographies, both science and non-science related ones. Of course, I also like art. All crystallographers like art.”

Wang relaxing with his younger son in upstate New York.

Profilee-at-a-Glance Institution New York University

Area of Research To understand how

membrane transporters work in atomic detail.