Structural Biology (Atsuko YAMASHITA)

Structural Biology Atsuko YAMASHITA, PhD

Major Areas of Research

1. Structural biology of membrane proteins important for pharmaceutical, medicinal, and dentistry researches
2. Structural biology of sensory systems
3. Research and development of methods to facilitate protein crystallization

Current Research Interests

We aim to elucidate functional mechanisms of membrane proteins important for pharmaceutical, medicinal, and dentistry researches, as well as proteins participating in sensory systems, by structural biology. The pivot of our study is structural analyses of these proteins by X-ray crystallography using SPring-8 beamlines. We also perform functional analyses of these proteins with biochemical and physiological approaches. The objective of our lab is to understand the biological systems maintained by these proteins in depth by integrating the structural and functional information. Sense, such as vision, audition, touch sensation, gustation, and olfaction, is the sole window opening toward the outside of our bodies: it is an important function for living organisms to receive, transduce, integrate, recognize and process a wide array of information from the environment. In this lab, we focus on the first step of sensing through signal reception from environment to signal transduction and transfer in a cell. We target sensory receptors, signaling proteins, and regulatory proteins, and aim to understand the sensing mechanisms. Membrane proteins, including sensory receptors, account for about a third of genomic products, and are responsible for many important biological reactions in our bodies. They are also important targets for drug discovery. We target receptors, channels, and transporters, important for pharmaceutical, medicinal, and dentistry researches, and aim to obtain important information for drug discovery. Many of our target proteins are eukaryotic membrane proteins, which are currently ones of the most difficult targets in the field of structural biology. In order to achieve structural analysis of these targets, we also carry out research and development of methods to facilitate sample preparation, a bottleneck for membrane protein crystallography. One of our strategies for this is taking advantage of the GFP-fusion technologies, recently pplied in screening of protein samples suitable for crystallization.

Selected Recent Publications

1. Ashikawa Y, Ihara M, Matsuura N, Fukunaga Y, Kusakabe Y, Yamashita A.: GFP-based evaluation system of recombinant expression through the secretory pathway in insect cells and its application to the extracellular domains of class C GPCRs. Protein Sci. (2011) 20, 1720-1734
2. Ihara M, Matsuura N, Yamashita A.: High-resolution Native-PAGE for membrane proteins capable of fluorescence detection and hydrodynamic-state evaluation. Anal. Biochem. (2011) 412, 217-223
3. Singh SK, Piscitelli CL, Yamashita A, Gouaux E.: A competitive inhibitor traps LeuT in an open-to-out conformation. Science (2008) 322, 1655-1661
4. Ihara M, Okajima T, Yamashita A, Oda T, Hirata K, Nishiwaki H, Morimoto T, Akamatsu M, Ashikawa Y, Kuroda S, Mega R, Kuramitsu S, Sattelle DB, Matsuda K.: Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides midacloprid and clothianidin. Invert Neurosci. (2008) 8, 71-81