The Role of FG Nucleoporins Amino Acid Sequence Composition in Nucleocytoplasmic Transport
نام عام مواد
[Thesis]
نام نخستين پديدآور
Peyro, Mohaddeseh
نام ساير پديدآوران
Mofrad, Mohammad R.K.
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
University of California, Berkeley
تاریخ نشرو بخش و غیره
2020
مشخصات ظاهری
نام خاص و کميت اثر
129
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
University of California, Berkeley
امتياز متن
2020
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
Bidirectional transport of molecules through the nuclear envelope (nucleocytoplasmic transport) is a vital, yet very complex process inside eukaryotic cells. This process is facilitated by thousands of nanoscale pores embedded in the nuclear envelope, named nuclear pore complexes (NPCs). The remarkable feature of NPC is that it facilitates transport in a fast, yet selective manner. Despite numerous studies, the underlying mechanism of NPC's function is unknown. The intricate function of NPC cannot be fully captured via experimental techniques due to small scale and rapid movement of the FG Nucleoporins, which are intrinsically disordered proteins rich in phenylalanine-glycine repeats, responsible for facilitating the transport process. In this dissertation, using a range of computational approaches, the role of FG Nups in the nuclear transport process is explored. FG Nups do not have a well-defined secondary structure and it is believed that their sequence composition and conformational ensemble are critical for their function in the NPC. In this dissertation, for the first time, specific sequence patterns in the charge distribution of FG Nups were identified that were not observed in other intrinsically disordered proteins. These patterns are extended sub-sequences that only contain positively charged residues, have low charge density, and are located toward the N-terminus of FG Nups. We named these evolutionarily conserved patterns like charge regions (LCRs). Additionally, the role that LCRs play in the conformational ensemble and function of FG Nups was examined, using coarse-grained molecular dynamics simulations. Our simulations in multiple levels (single Nups, ring cross sections of NPC, and whole NPC) show that number of charged residues in the LCR impact the conformational ensemble of FG Nups and movement of the cargo complex. Our simulations also suggest that the number of charged residues in LCR can regulate the interaction of cargo complex with FG Nups. Since conformational ensemble of FG Nups and their interaction with cargo complex are two governing factors of the transport process, we suggest that LCRs, the unique and evolutionarily conserved features of FG Nups, are major regulators of the nucleocytoplasmic transport.
موضوع (اسم عام یاعبارت اسمی عام)
موضوع مستند نشده
Bioengineering
موضوع مستند نشده
Bioinformatics
موضوع مستند نشده
Biophysics
موضوع مستند نشده
Molecular physics
موضوع مستند نشده
Nanoscience
موضوع مستند نشده
Nuclear physics
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )