Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/3685

Identification and characterization of a novel family of transmembrane and coiled-coil proteins

Authors Kho, Yik Shing
Issue Date 2008
Summary Endoplasmic reticulum (ER) is a single membrane system composed of structurally and functionally distinct domains, including the nuclear envelope, the rough ER (RER), and the smooth ER (SER). The diversity of ER structure parallels its many functions such as protein synthesis, lipid synthesis, protein quality control, Ca2+ signaling, and protein translocation. We have identified a family of novel proteins named transmembrane and coiled-coil proteins (TMCCs). In human, the TMCC family contains at least three members (TMCC1, 2 and 3), which are transcribed from chromosome 3, 1 and 12, respectively. Sequence alignment revealed that these proteins share high sequence homology in three regions, the middle region (225-315 of TMCC1), the coiled-coil region (310-575 of TMCC1), and the transmembrane region (571-653 of TMCC1). These regions are evolutionarily conserved in a range of organisms from C. elegans to human. In this thesis work, we focus on the characterization of TMCC1. TMCC1 is expressed in all tissues and cell lines examined. Immunofluoresence imaging and biochemical subcellular fractionation revealed that TMCC1 localizes to the ER. We also investigated the functions of the three conserved regions. First, the C-terminal transmembrane domain region (571-653 of TMCC1) is responsible for ER targeting. In addition, the tail region interacts with a number of proteins including nucleocytoplasmic transporters. Second, the TMCC proteins can interact with each other via the conserved coiled-coil domain (460-575). Third, TMCC1 interacts with ribosomal proteins using the middle region (225-315). Similar properties were observed from TMCC2 and TMCC3. Taken together, TMCCs are a novel family of ER resident proteins that interacts with ribosome and nucleocytoplasmic trafficking proteins. Our results suggest that TMCCs may play a role in ribosome recruitment to the ER, ribosome transport across the nuclear envelope, ribosome maturation, and maintenance of the protein translation efficiency.
Note Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2008
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Language English
Format Thesis
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