東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Sorting signals, domain conformation...

Roy, Gargi.

FindBook

Google Book

Amazon

博客來

Sorting signals, domain conformation and interdomain interactions in CFTR misprocessing and rescue.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Sorting signals, domain conformation and interdomain interactions in CFTR misprocessing and rescue./
作者:	Roy, Gargi.
面頁冊數:	116 p.
附註:	Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3449.
Contained By:	Dissertation Abstracts International71-06B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407728
ISBN:	9781124016122

Sorting signals, domain conformation and interdomain interactions in CFTR misprocessing and rescue.
Roy, Gargi.

Sorting signals, domain conformation and interdomain interactions in CFTR misprocessing and rescue. - 116 p.

Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3449.

Thesis (Ph.D.)--The University of Toledo, 2010.

Cystic fibrosis (CF) is among the most common lethal inherited diseases in the US. The deletion of phenylalanine at residue 508 (DeltaF508) within cystic fibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation. DeltaF508 mutant is unable to exit the endoplasmic reticulum (ER). The precise mechanism of the defective ER-to-Golgi export of DeltaF508 CFTR is not known. A di-acidic ER exit code (DAD) has been identified within the first nucleotide binding domain (NBD1) of CFTR. Disruption of this motif leads to the defective coupling of CFTR to the COPII machinery and the subsequent impaired export of CFTR from the ER. We performed a systematic analysis of the sorting signals, domain conformation and inter-domain interactions of CFTR in presence of DeltaF508 mutation and during its rescue by low temperature or second site mutation (R555K). We found that rescue of DeltaF508 CFTR depends on the DAD motif within the NBD1. Disruption of DAD (DAA) reduces the Sec24 association of DeltaF508 CFTR whereas rescue mutation R555K increases it. Using in situ limited proteolysis we identified conformational defects in N-terminal region and NBD1 in DeltaF508 CFTR. DeltaF508 rescue is accompanied by global conformational reversion. Further domain-domain interactions within CFTR play an important role in both DeltaF508 CFTR misprocessing and rescue. Our data firmly establish that while DAA is an exit code mutant DeltaF508 CFTR has widespread conformational defect which compromises its export and stability. Restoration of its global conformation leads to restoration of its export as well as function.

ISBN: 9781124016122Subjects--Topical Terms:

1017730
Biology, Genetics.

Sorting signals, domain conformation and interdomain interactions in CFTR misprocessing and rescue.
LDR:02528nam 2200265 4500 001 1402994
005 20111108080343.5
008 130515s2010 ||||||||||||||||| ||eng d
020 $a 9781124016122
035 $a (UMI)AAI3407728
035 $a AAI3407728
040 $a UMI $c UMI
100 1 $a Roy, Gargi. $3 1682225
245 1 0 $a Sorting signals, domain conformation and interdomain interactions in CFTR misprocessing and rescue.
300 $a 116 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3449.
500 $a Adviser: Xiaodong Wang.
502 $a Thesis (Ph.D.)--The University of Toledo, 2010.
520 $a Cystic fibrosis (CF) is among the most common lethal inherited diseases in the US. The deletion of phenylalanine at residue 508 (DeltaF508) within cystic fibrosis transmembrane conductance regulator (CFTR) is the most common CF causing mutation. DeltaF508 mutant is unable to exit the endoplasmic reticulum (ER). The precise mechanism of the defective ER-to-Golgi export of DeltaF508 CFTR is not known. A di-acidic ER exit code (DAD) has been identified within the first nucleotide binding domain (NBD1) of CFTR. Disruption of this motif leads to the defective coupling of CFTR to the COPII machinery and the subsequent impaired export of CFTR from the ER. We performed a systematic analysis of the sorting signals, domain conformation and inter-domain interactions of CFTR in presence of DeltaF508 mutation and during its rescue by low temperature or second site mutation (R555K). We found that rescue of DeltaF508 CFTR depends on the DAD motif within the NBD1. Disruption of DAD (DAA) reduces the Sec24 association of DeltaF508 CFTR whereas rescue mutation R555K increases it. Using in situ limited proteolysis we identified conformational defects in N-terminal region and NBD1 in DeltaF508 CFTR. DeltaF508 rescue is accompanied by global conformational reversion. Further domain-domain interactions within CFTR play an important role in both DeltaF508 CFTR misprocessing and rescue. Our data firmly establish that while DAA is an exit code mutant DeltaF508 CFTR has widespread conformational defect which compromises its export and stability. Restoration of its global conformation leads to restoration of its export as well as function.
590 $a School code: 0232.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 $a The University of Toledo. $3 1023352
773 0 $t Dissertation Abstracts International $g 71-06B.
790 1 0 $a Wang, Xiaodong, $e advisor
790 $a 0232
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407728