語系:
繁體中文
English
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
Defining a regulatory role for the H...
~
Shelly, Spencer S.
FindBook
Google Book
Amazon
博客來
Defining a regulatory role for the HSV glycoprotein B membrane proximal region in membrane association.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
Defining a regulatory role for the HSV glycoprotein B membrane proximal region in membrane association./
作者:
Shelly, Spencer S.
面頁冊數:
180 p.
附註:
Source: Dissertation Abstracts International, Volume: 75-01(E), Section: B.
Contained By:
Dissertation Abstracts International75-01B(E).
標題:
Biology, Virology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3594852
ISBN:
9781303396748
Defining a regulatory role for the HSV glycoprotein B membrane proximal region in membrane association.
Shelly, Spencer S.
Defining a regulatory role for the HSV glycoprotein B membrane proximal region in membrane association.
- 180 p.
Source: Dissertation Abstracts International, Volume: 75-01(E), Section: B.
Thesis (Ph.D.)--University of Pennsylvania, 2013.
Herpes simplex virus (HSV) entry requires four essential glycoproteins (gD, gH/gL, and gB) to enable fusion between the virion envelope and the cellular membrane. The fusion cascade is activated by gD binding to one of its receptors, nectin-1 or HVEM. Glycoprotein B (gB), a class III viral fusion protein, mediates the fusion reaction, while data indicates that gH/gL acts as a regulator of gB. gB is trimeric and has a 773 amino acid ectodomain with a highly hydrophobic membrane proximal region (MPR) (residues 731-773) and two fusion loops (FL) per protomer. The post-fusion structure of gB was solved from the gB(730t) construct, which is truncated to remove the hydrophobic MPR residues. In this dissertation I investigated the MPRs influence on gBs ability to interact with membranes. I hypothesize that the MPR regulates fusion loop exposure by interacting with the fusion loops and masks them until fusion begins. To investigate this process I constructed a series of MPR deletion, truncation, and point mutations using both full-length mammalian expression vectors and purified baculovirus expressed protein. I found that deletions in the MPR from full-length gB resulted in a disruption in cell surface expression in transfected cells. This suggests the MPR is necessary for proper folding or transport of gB. Soluble gB MPR truncations [gB(759t), gB(749t), gB(739t)] were expressed and purified using the baculovirus expression system, and compared to MPR-less gB(730t) and full MPR containing gB(773t). I found that gB containing an MPR segment were all compromised in their ability to bind liposomes in comparison to gB(730t), which lacks any MPR residues. Supporting our hypothesis we found that residues 731 to 739 were sufficient prevent liposome association and mutation of two aromatic residues, F732 and F739, to alanine in gB(739t) restored gBs ability to bind liposomes. Together, my data suggests the MPR does indeed regulate gBs ability to associate with liposomes, and that aromatic residues in the MPR are important for this function. This supports our model that the MPR masks the gB FLs to prevent premature membrane association and adds another layer of regulation to the HSV entry cascade.
ISBN: 9781303396748Subjects--Topical Terms:
1019068
Biology, Virology.
Defining a regulatory role for the HSV glycoprotein B membrane proximal region in membrane association.
LDR
:03156nam a2200277 4500
001
1965089
005
20141010093000.5
008
150210s2013 ||||||||||||||||| ||eng d
020
$a
9781303396748
035
$a
(MiAaPQ)AAI3594852
035
$a
AAI3594852
040
$a
MiAaPQ
$c
MiAaPQ
100
1
$a
Shelly, Spencer S.
$3
2101693
245
1 0
$a
Defining a regulatory role for the HSV glycoprotein B membrane proximal region in membrane association.
300
$a
180 p.
500
$a
Source: Dissertation Abstracts International, Volume: 75-01(E), Section: B.
500
$a
Advisers: Roselyn J. Eisenberg; Gary H. Cohen.
502
$a
Thesis (Ph.D.)--University of Pennsylvania, 2013.
520
$a
Herpes simplex virus (HSV) entry requires four essential glycoproteins (gD, gH/gL, and gB) to enable fusion between the virion envelope and the cellular membrane. The fusion cascade is activated by gD binding to one of its receptors, nectin-1 or HVEM. Glycoprotein B (gB), a class III viral fusion protein, mediates the fusion reaction, while data indicates that gH/gL acts as a regulator of gB. gB is trimeric and has a 773 amino acid ectodomain with a highly hydrophobic membrane proximal region (MPR) (residues 731-773) and two fusion loops (FL) per protomer. The post-fusion structure of gB was solved from the gB(730t) construct, which is truncated to remove the hydrophobic MPR residues. In this dissertation I investigated the MPRs influence on gBs ability to interact with membranes. I hypothesize that the MPR regulates fusion loop exposure by interacting with the fusion loops and masks them until fusion begins. To investigate this process I constructed a series of MPR deletion, truncation, and point mutations using both full-length mammalian expression vectors and purified baculovirus expressed protein. I found that deletions in the MPR from full-length gB resulted in a disruption in cell surface expression in transfected cells. This suggests the MPR is necessary for proper folding or transport of gB. Soluble gB MPR truncations [gB(759t), gB(749t), gB(739t)] were expressed and purified using the baculovirus expression system, and compared to MPR-less gB(730t) and full MPR containing gB(773t). I found that gB containing an MPR segment were all compromised in their ability to bind liposomes in comparison to gB(730t), which lacks any MPR residues. Supporting our hypothesis we found that residues 731 to 739 were sufficient prevent liposome association and mutation of two aromatic residues, F732 and F739, to alanine in gB(739t) restored gBs ability to bind liposomes. Together, my data suggests the MPR does indeed regulate gBs ability to associate with liposomes, and that aromatic residues in the MPR are important for this function. This supports our model that the MPR masks the gB FLs to prevent premature membrane association and adds another layer of regulation to the HSV entry cascade.
590
$a
School code: 0175.
650
4
$a
Biology, Virology.
$3
1019068
650
4
$a
Biology, General.
$3
1018625
690
$a
0720
690
$a
0306
710
2
$a
University of Pennsylvania.
$b
Cell and Molecular Biology.
$3
2101694
773
0
$t
Dissertation Abstracts International
$g
75-01B(E).
790
$a
0175
791
$a
Ph.D.
792
$a
2013
793
$a
English
856
4 0
$u
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3594852
筆 0 讀者評論
館藏地:
全部
電子資源
出版年:
卷號:
館藏
1 筆 • 頁數 1 •
1
條碼號
典藏地名稱
館藏流通類別
資料類型
索書號
使用類型
借閱狀態
預約狀態
備註欄
附件
W9260088
電子資源
11.線上閱覽_V
電子書
EB
一般使用(Normal)
在架
0
1 筆 • 頁數 1 •
1
多媒體
評論
新增評論
分享你的心得
Export
取書館
處理中
...
變更密碼
登入