Ph.D. Institute of Biophysics, Chinese Academy of Sciences, Beijing, P. R. China, 1999
Emory University, Atlanta, GA, 2007
University of California at San Diego, La Jolla, CA, 2002
Accepting new MS students in 2022: Yes (BMB)
Accepting new PhD students in 2022: Yes (BMB)
4340 Scott Hall
Structure and function of SET and MYND domain-containing (SMYD) proteins.
How the “marriage” between SET and MYND domains made SMYD proteins so special
SMYD proteins are a special class of protein lysine methyltransferases with an MYND domain inserted into a SET domain. Structurally, these two functional domains are intimately bundled, with a conserved architecture and being integrated into a single coherent structural module. The evolutionary history of SMYD proteins is dated back to at least 1.5 billion years ago at the beginning of eukaryotic life. They are present in both vertebrate and invertebrate animals. They are also present in choanoflagellates. Choanoflagellates are a group of free-living unicellular eukaryotes and considered to be the closest living unicellular relatives of the animals. SMYD proteins are also present in both higher and lower plants: the higher plants such as Arabidopsis thaliana, soy bean, and corn; the lower plants such as Ostreococcus tauri. Ostreococcus tauri is a marine green algae, unicellular, and is the smallest free-living eukaryote yet described. SMYD proteins are also present in amoeba. Amoeba are a group of single-celled organisms that possess pseudopods or move by protoplasmic flow. So you can see, SMYD proteins are conserved across eukaryotic species, from simple, single-celled organisms to more complex multicellular life, from marine organisms to land species, and from sessile plants to motile animals. A suggestion from this wide presence is: SMYD proteins are functionally important and might be involved in some core biological processes that are conserved in eukaryotes.
However, what selective pressure has driven the “marriage” of the SET and MYND domains and what specific function has evolved at the time of this marriage, remain unclear. From the time when SMYD1, the founding member of the SMYD protein family, was identified as being required for cardiomyocyte differentiation, our understanding of the structure and function of SMYD proteins has been steadily increasing. To date, we have known that not only are they involved in heart and skeletal muscle development, but also have diverse other roles in both normal biology and disease states, ranging from tumor cell proliferation, cancer stemness and dormancy, the immune response, to a very recent association with ciliogenesis via regulating microtubule dynamics. While the scope of SMYD protein research has been broadened significantly over the past two decades, it is becoming increasingly clear to us that the more we learn about their multifunctionality and multispecificity, the more we realize that there are more yet to be discovered. With the thriving of functional genomics studies, new research ideas are emerging in uncharted areas, including but not limited to mitochondrial and nucleolar ribosome biogenesis, RNA biology in stress granules, intellectual disability, calcium-dependent signaling, as well as sperm chromatin remodeling at fertilization.
The main goal of our research is to uncover new paradigms in SMYD protein research while further broadening our understanding of their functional diversity. As our knowledge develops and advances, we want to conclude that the marriage between the SET and MYND domains that made SMYD proteins so special is an ultimate rule governing their past, present and future.
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