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The structural and functional study ...

The University of Tennessee Health Science Center., Molecular Sciences.

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The structural and functional study of GIT1 paxillin binding domain.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The structural and functional study of GIT1 paxillin binding domain./
作者:	Zhang, Ziwei.
面頁冊數:	153 p.
附註:	Adviser: Jie Zheng.
Contained By:	Dissertation Abstracts International69-03B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3297867
ISBN:	9780549491958

The structural and functional study of GIT1 paxillin binding domain.
Zhang, Ziwei.

The structural and functional study of GIT1 paxillin binding domain. - 153 p.

Adviser: Jie Zheng.

Thesis (Ph.D.)--The University of Tennessee Health Science Center, 2008.

The G protein coupled receptor (GPCR)-kinase (GRK) interacting protein 1 (GIT1) is a multidomain protein that plays an important role in cell adhesion, motility, cytoskeletal remodeling, and membrane trafficking. GIT1 mediates the localization of p21-activated kinase (PAK) and PAK-interactive exchange factor (PIX) to focal adhesions, and its activation is regulated by the interaction between its C terminal paxillin-binding domain (PBD) and the LD motifs of paxillin.

ISBN: 9780549491958Subjects--Topical Terms:

1017719
Biology, Molecular.

The structural and functional study of GIT1 paxillin binding domain.
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020 $a 9780549491958
035 $a (UMI)AAI3297867
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040 $a UMI $c UMI
100 1 $a Zhang, Ziwei. $3 1030187
245 1 4 $a The structural and functional study of GIT1 paxillin binding domain.
300 $a 153 p.
500 $a Adviser: Jie Zheng.
500 $a Source: Dissertation Abstracts International, Volume: 69-03, Section: B, page: 1478.
502 $a Thesis (Ph.D.)--The University of Tennessee Health Science Center, 2008.
520 $a The G protein coupled receptor (GPCR)-kinase (GRK) interacting protein 1 (GIT1) is a multidomain protein that plays an important role in cell adhesion, motility, cytoskeletal remodeling, and membrane trafficking. GIT1 mediates the localization of p21-activated kinase (PAK) and PAK-interactive exchange factor (PIX) to focal adhesions, and its activation is regulated by the interaction between its C terminal paxillin-binding domain (PBD) and the LD motifs of paxillin.
520 $a In this dissertation, we determined the solution structure of rat GIT1 PBD by nuclear magnetic resonance (NMR) spectroscopy. The PBD folds into a four-helix bundle, which is structurally similar to the focal adhesion targeting (FAT) domain and the vinculin tail (Vt) domain. The PBD is more stable than the FAT domain and there is no evidence of helix 1 swapping.
520 $a Previous studies showed that GIT1 interacts with paxillin through the LD4 motif. However, studies in this dissertation demonstrated that in addition to the LD4 motif, the GIT1 PBD can also bind to the paxillin LD2 motif; and both LD2 and LD4 motifs competitively target the same site on the PBD surface. This dissertation also probed the function of paxillin splice variants by comparing their interaction with GIT1 PBD. It seems the paxillin isoforms did not play an important role in determining the affinity to GIT1. We also revealed that paxillin S272 phosphorylation does not influence GIT1 PBD binding in vitro. These results are in agreement with the notion that phosphorylation of paxillin S272 plays an essential role in regulating focal adhesion turnover.
520 $a This dissertation also computationally derived the complex structures of GIT1 PBD bound with either LD2 peptide or LD4 peptide, based on the experimental binding site information. The LD2 and LD4 peptides bound to GIT1 PBD in a manner similar to the crystal structure of FAT-LD2 complex. The complex structures visualized the reason why both LD2 and LD4 can bind to the same GIT1 binding site. It also addressed the specificity problem in determining paxillin binding to GIT1 versus FAK.
520 $a Our finding reconciles the controversial observations of earlier studies and provides a clearer picture of focal adhesion regulation. The structural studies of GIT1 PBD presented in this dissertation shed more light on the understanding of GIT functions. The novel findings also allow us to propose a working model regarding FA disassembly.
590 $a School code: 0783.
650 4 $a Biology, Molecular. $3 1017719
650 4 $a Biophysics, Medical. $3 1017681
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0307
690 $a 0487
690 $a 0760
710 2 $a The University of Tennessee Health Science Center. $b Molecular Sciences. $3 1025227
773 0 $t Dissertation Abstracts International $g 69-03B.
790 $a 0783
790 1 0 $a Morris, Stephan W. $e committee member
790 1 0 $a Nelson, David R. $e committee member
790 1 0 $a Senogles, Susan E. $e committee member
790 1 0 $a White, Stephen W. $e committee member
790 1 0 $a Zheng, Jie, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3297867