東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Conformational dynamics of interleuk...

Anderson, William David.

Linked to FindBook

Google Book

Amazon

博客來

Conformational dynamics of interleukin-1beta and protein-membrane interactions.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Conformational dynamics of interleukin-1beta and protein-membrane interactions./
Author:	Anderson, William David.
Description:	142 p.
Notes:	Adviser: Patricia A. Jennings.
Contained By:	Dissertation Abstracts International68-01B.
Subject:	Chemistry, Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3249669

Conformational dynamics of interleukin-1beta and protein-membrane interactions.
Anderson, William David.

Conformational dynamics of interleukin-1beta and protein-membrane interactions. - 142 p.

Adviser: Patricia A. Jennings.

Thesis (Ph.D.)--University of California, San Diego, 2007.

Interleukin-1beta is a cytokine central in the immunological response to injury and infection. While the structure is well known, the (i) modulating effects of point mutations upon function and the (ii) process of post-translational export remain poorly understood. In the first part of the dissertation, the effects of several mutations important in protein folding and function, are examined. Water specific NMR experiments show the sites of hydrogen-bound water molecules in the beta-trefoil fold of IL-1beta. The structural hydration of several mutants with varying functional and folding propensities was found to be the same as wild-type, showing that the structural water interactions are robust. The conformational dynamics of the wild-type and two destabilized Thr-9 mutants were further explored using native state hydrogen exchange (NHX) NMR spectroscopy. The NHX experiments highlight the destabilizing effects of the T9Q and T9G mutations, yet the residue specific nature of NMR spectroscopy allowed the mapping of destabilizing, non-destabilizing, and hyper-stabilizing effects across the IL-1beta protein to sites distal from the mutation. These results are discussed in light of computational modeling of the T9G mutation.Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Conformational dynamics of interleukin-1beta and protein-membrane interactions.
LDR:03304nam 2200277 a 45 001 939210
005 20110512
008 110512s2007 ||||||||||||||||| ||eng d
035 $a (UMI)AAI3249669
035 $a AAI3249669
040 $a UMI $c UMI
100 1 $a Anderson, William David. $3 1263205
245 1 0 $a Conformational dynamics of interleukin-1beta and protein-membrane interactions.
300 $a 142 p.
500 $a Adviser: Patricia A. Jennings.
500 $a Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0269.
502 $a Thesis (Ph.D.)--University of California, San Diego, 2007.
520 $a Interleukin-1beta is a cytokine central in the immunological response to injury and infection. While the structure is well known, the (i) modulating effects of point mutations upon function and the (ii) process of post-translational export remain poorly understood. In the first part of the dissertation, the effects of several mutations important in protein folding and function, are examined. Water specific NMR experiments show the sites of hydrogen-bound water molecules in the beta-trefoil fold of IL-1beta. The structural hydration of several mutants with varying functional and folding propensities was found to be the same as wild-type, showing that the structural water interactions are robust. The conformational dynamics of the wild-type and two destabilized Thr-9 mutants were further explored using native state hydrogen exchange (NHX) NMR spectroscopy. The NHX experiments highlight the destabilizing effects of the T9Q and T9G mutations, yet the residue specific nature of NMR spectroscopy allowed the mapping of destabilizing, non-destabilizing, and hyper-stabilizing effects across the IL-1beta protein to sites distal from the mutation. These results are discussed in light of computational modeling of the T9G mutation.
520 $a In the second part of the dissertation, protein-lipid interactions are explored, beginning with the novel finding of a weak but highly specific interaction between IL-1beta and phospholipid bicelles in solution. NHX NMR spectroscopy shows the destabilization of IL-1beta in the presence of bicelles. A combination of chemical shift analysis, heteronuclear 1H-15 N NOEs, and paramagnetic relaxation enhancement identified a contiguous surface on one side of the molecule as the putative site of interaction with bicelles. These results represent the first structural evidence of a membrane-protein interaction of IL-1beta, and are discussed in light of the hypothesized non-classical secretion of IL-1beta. Finally, we have implemented transferred cross-saturation NMR experiments using the transmembrane Pf1 filamentous phage coat protein in isotropic bicelles. Protein residues can be localized to the core of the bicelle or the aqueous interface via selective pre-saturation of the o-methyl or choline-methyl protons, respectively. Methyl-proton specific TCS in isotropic bicelles is an effective and simple method for characterizing the transmembrane region of proteins.
590 $a School code: 0033.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0487
690 $a 0982
710 2 $a University of California, San Diego. $3 1018093
773 0 $t Dissertation Abstracts International $g 68-01B.
790 $a 0033
790 1 0 $a Jennings, Patricia A., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3249669