Neuronal structural biology is the focus area of our laboratory. We aim to understand the molecular mechanisms governing synaptic signal transduction complex organization, dynamic regulations of synaptic complex assemblies, and trafficking of proteins involved in synaptic signaling using a combination of NMR spectroscopy, X-ray crystallography, biochemistry, molecular biology and cell biology approaches. The second focus of the lab is to elucidate the molecular basis of protein complexes regulating cell polarity establishment and maintenance.

In the first area, we are primarily working on synaptic signal transduction complex organizations by various scaffold proteins (e.g. PDZ domain proteins). In postsynaptic neurons, signal transduction complexes are often organized into large multi-components assemblies (transducisomes). The proper organization of such supramolecular complexes is critical for specificity and efficiency of signal transmissions across synapses. We are also interested in the dynamics of various signaling complex assemblies, by investigating regulated protein-protein interactions in synapses.

In the second area, we are interested in how protein complexes (e.g. the Par-3/Par-6/aPKC complex and the Usher complex) orchestrate the highly polarized nature of a wide variety of eukaryotic cells including neurons and epithelia. Our prime interest is to understand, from structural and biochemical angles, how these complexes assemble with other cell polarity proteins and lipids in controlling cell polarity. We are also interested in why mutations of polarity proteins are linked with human diseases.

Zhu, J., Shang, Y., Chen, J., and Zhang, M. (2012) "Structure and Function of the Guanylate Kinase-like Domain of the MAGUK Family Scaffold Proteins." Frontiers in Biology