國立虎尾科技大學 |

Programmed Secretion Arrest and Receptor-Triggered Restart of CdiA during Contact-Dependent Growth Inhibition.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Programmed Secretion Arrest and Receptor-Triggered Restart of CdiA during Contact-Dependent Growth Inhibition./
作者:	Song, Kiho.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	190 p.
附註:	Source: Dissertations Abstracts International, Volume: 82-04, Section: B.
Contained By:	Dissertations Abstracts International82-04B.
標題:	Gram-negative bacteria. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28031299
ISBN:	9798684681561

Programmed Secretion Arrest and Receptor-Triggered Restart of CdiA during Contact-Dependent Growth Inhibition.
Song, Kiho.

Programmed Secretion Arrest and Receptor-Triggered Restart of CdiA during Contact-Dependent Growth Inhibition. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 190 p.

Source: Dissertations Abstracts International, Volume: 82-04, Section: B.

Thesis (Ph.D.)--University of California, Santa Barbara, 2020.

This item must not be sold to any third party vendors.

Many Gram-negative bacteria utilize contact-dependent growth inhibition (CDI) systems to deliver toxins to nearby cells using a large (~350kD) filamentous protein, CdiA, expressed on their cell surface. Recently, we discovered that biogenesis of CdiA is tightly regulated such that the N-terminal half of CdiA is first exported to form a 33nm stick on the cell surface, while the C-terminal half remains in the periplasm. When CdiA recognizes a receptor on a neighboring cell, the periplasmic half resumes secretion and penetrates the neighboring cell’s outer membrane to deliver the C-terminal toxin domain. This mode of programmed secretion is crucial for CdiA function because prematurely secreting its C-terminal half releases CdiA off the cell surface and renders it ineffective. Since there is no obvious source of energy or potential difference across the outer membrane, it is intriguing how secretion of a large protein like CdiA is arrested at a precise configuration only to be resumed by a receptor-binding event. This thesis will highlight the recent findings about this mechanism of programmed secretion of CdiA. Deletions and sequence-replacement mutants have identified a 50-residue long, Tyr-Pro enriched, region in the periplasmic half of the protein responsible for secretion arrest. The CdiA receptor-binding event specifically relays a signal to release this arrest and resume secretion. Studies with a chimeric CdiA-DHFR have shown that the periplasmic CdiA domain must first unfold in order to resume export. Substrate-induced folding of the periplasmic DHFR fusion disrupts secretion restart. Interestingly, enzymatic fusions to CdiA demonstrate that the system functions as a nanoscale switch to direct the enzymatic activity to the extracellular space only when CdiA binds a receptor. Lastly, the filamentous N-terminal CdiA is a robust toxin delivery machine which tolerates shortening and severing at its base.

ISBN: 9798684681561Subjects--Topical Terms:

883892
Gram-negative bacteria.
Subjects--Index Terms:

Bacterial competition

Programmed Secretion Arrest and Receptor-Triggered Restart of CdiA during Contact-Dependent Growth Inhibition.
LDR:03225nam a2200409 4500 001 1121838
005 20240624103648.5
006 m o d
007 cr#unu||||||||
008 240823s2020 ||||||||||||||||| ||eng d
020 $a 9798684681561
035 $a (MiAaPQ)AAI28031299
035 $a AAI28031299
040 $a MiAaPQ $c MiAaPQ
100 1 $a Song, Kiho. $3 1437631
245 1 0 $a Programmed Secretion Arrest and Receptor-Triggered Restart of CdiA during Contact-Dependent Growth Inhibition.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 190 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-04, Section: B.
500 $a Advisor: Hayes, Christopher S.
502 $a Thesis (Ph.D.)--University of California, Santa Barbara, 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Many Gram-negative bacteria utilize contact-dependent growth inhibition (CDI) systems to deliver toxins to nearby cells using a large (~350kD) filamentous protein, CdiA, expressed on their cell surface. Recently, we discovered that biogenesis of CdiA is tightly regulated such that the N-terminal half of CdiA is first exported to form a 33nm stick on the cell surface, while the C-terminal half remains in the periplasm. When CdiA recognizes a receptor on a neighboring cell, the periplasmic half resumes secretion and penetrates the neighboring cell’s outer membrane to deliver the C-terminal toxin domain. This mode of programmed secretion is crucial for CdiA function because prematurely secreting its C-terminal half releases CdiA off the cell surface and renders it ineffective. Since there is no obvious source of energy or potential difference across the outer membrane, it is intriguing how secretion of a large protein like CdiA is arrested at a precise configuration only to be resumed by a receptor-binding event. This thesis will highlight the recent findings about this mechanism of programmed secretion of CdiA. Deletions and sequence-replacement mutants have identified a 50-residue long, Tyr-Pro enriched, region in the periplasmic half of the protein responsible for secretion arrest. The CdiA receptor-binding event specifically relays a signal to release this arrest and resume secretion. Studies with a chimeric CdiA-DHFR have shown that the periplasmic CdiA domain must first unfold in order to resume export. Substrate-induced folding of the periplasmic DHFR fusion disrupts secretion restart. Interestingly, enzymatic fusions to CdiA demonstrate that the system functions as a nanoscale switch to direct the enzymatic activity to the extracellular space only when CdiA binds a receptor. Lastly, the filamentous N-terminal CdiA is a robust toxin delivery machine which tolerates shortening and severing at its base.
590 $a School code: 0035.
650 4 $a Gram-negative bacteria. $3 883892
650 4 $a Microbiology. $3 591510
650 4 $a Biochemistry. $3 582831
650 4 $a Molecular biology. $3 583443
653 $a Bacterial competition
653 $a CDI
653 $a CdiA
653 $a Protein secretion
653 $a TPS
653 $a Type V secretion system
690 $a 0307
690 $a 0487
690 $a 0410
710 2 $a University of California, Santa Barbara. $b Biomolecular Science and Engineering. $3 1437632
773 0 $t Dissertations Abstracts International $g 82-04B.
790 $a 0035
791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28031299