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Interaction of secretory protein seca with its binding partners: Lipids and SecB

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  1. Tez No: 403023
  2. Yazar: BAHAR TUBA FINDIK
  3. Danışmanlar: DR. LINDA RANDALL
  4. Tez Türü: Doktora
  5. Konular: Tıbbi Biyoloji, Medical Biology
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2016
  8. Dil: İngilizce
  9. Üniversite: University of Missouri
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 166

Özet

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Özet (Çeviri)

Thirty percent of proteins synthesized in the cytoplasm of E.coli are exported across or into the cytoplasmic membrane to reach their final destinations. The general secretory system exports precursor proteins through the heterotrimeric integral membrane protein complex, SecYEG, with the help of the myriad interactions that occur among SecA, the ATPase, SecB, the cytosolic chaperone, precursor and membrane. For efficient translocation, many precursor proteins are dependent on the chaperone SecB, which facilitates export by maintaining polypeptides in a nonnative conformation. In this thesis, we describe three projects. Two are completed, and the third is still in progress. The first one, described in Chapter 2, reports the chromosomal level of SecB in E.coli, giving the details for proper preparation of standards for quantitative immunoblotting. In Chapter 3, we investigated the interaction of SecA with lipids. We used three model systems: liposomes, liposomes assembled with SecYEG either alone or in the complex with SecA. We showed that the N-terminal ten residues of SecA interact with lipids integrally and these residues lie parallel to the plane of the membrane with a 6 Å maximal depth of penetration into the bilayer. We also observed that these 10 residues in the membrane display a helical pattern that has a periodicity close to that of a π helix. The other binding partner of SecA is SecB. When precursor-bound SecB interacts with two protomers of SecA, the precursor protein is trapped between the SecA and SecB in the complex, like a sandwich. Thus, transfer of the precursor presents an interesting topological problem. Nothing is known about the molecular details of the transfer of precursor along this pathway. In the project, described in Chapter four and still under investigation, we are trying to address the specific roles of each of the interaction sites of SecA:SecB complex. This knowledge will help us to elucidate the details of release of precursor within the complex. Current results indicate that the lack of the interaction between the N-terminal region of SecA with lipids results in a decrease in the rate constant of translocation; whereas, the interaction between the N-terminal region of SecA and the tail site of SecB has the greatest impact on the level of translocation.

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