کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5914560 | 1162743 | 2012 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification and structural basis for a novel interaction between Vav2 and Arap3
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کلمات کلیدی
GEFSH2VAV2ARAP3NMR - تشدید مغناطیسی هستهای SH2 domain - دامنه SH2Molecular dynamics - دینامیک ملکولی یا پویایی مولکولیComplex structure - ساختار پیچیدهGAP - شکافguanine nucleotide exchange factor - فاکتور تبادل نوکلئوتید گوانینPervanadate - فرانسویphosphotyrosine - فسفاتیزینSrc Homology 2 - همبستگی Src 2GTPase-activating protein - پروتئین فعال GTPase
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Vav2 is a ubiquitous guanine nucleotide exchange factor (GEF) for the small GTPase Rac1. It regulates processes including cell migration, neuronal development and phagocytosis through interactions with different proteins. In this study, Arap3, a dual GTPase-activating protein (GAP) for RhoA and Arf6, was first identified to be a novel interaction partner for Vav2 both in vitro and in vivo. ITC and NMR chemical shift perturbation experiments demonstrated that Vav2 SH2 domain was able to interact directly with phosphorylated Y1403 and Y1408 within the C-terminal region of Arap3 with high affinities, with the dissociation constants (Kd) of â¼0.27 and â¼1.40 μM, respectively. In addition, using different phosphotyrosine peptides, the pY +3 specificity of Vav2 SH2 domain was discovered. The solution structures of Vav2 SH2 domain in free and in complex with the phosphotyrosine peptide pY1408 were therefore determined to understand the structural basis of this recognition specificity. Structural analysis revealed that the presence of a Phe residue in the BG loop (BG6) leads to the formation of a shallow hydrophobic pY +3 pocket on the surface of Vav2 SH2 domain, which determines the pY +3 specificity of Vav2 SH2 domain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 180, Issue 1, October 2012, Pages 84-95
Journal: Journal of Structural Biology - Volume 180, Issue 1, October 2012, Pages 84-95
نویسندگان
Bo Wu, Fengsong Wang, Jiahai Zhang, Zhiyong Zhang, Liying Qin, Junhui Peng, Fudong Li, Jianping Liu, Guowei Lu, Qingguo Gong, Xuebiao Yao, Jihui Wu, Yunyu Shi,