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游离H、N和C-Grb2-SH2结构域的核磁共振归属

NMR assignment of free H, N and C-Grb2-SH2 domain.

作者信息

Sanches Karoline, Caruso Ícaro P, Almeida Fábio C L, Melo Fernando A

机构信息

Multiuser Center for Biomolecular Innovation (CMIB), Department of Physics, São Paulo State University (UNESP), São José Do Rio Preto, São Paulo, Brazil.

Institute of Medical Biochemistry (IBqM) and National Center of Nuclear Magnetic Resonance (CNRMN), Center for Structural Biology and Bioimaging (CENABIO), Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Biomol NMR Assign. 2019 Oct;13(2):295-298. doi: 10.1007/s12104-019-09894-x. Epub 2019 Apr 26.

Abstract

Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein composed of three domains, an N-terminal SH3 (nSH3), SH2 and a C-terminal SH3 (cSH3) domains. This multi-domain protein has been reported to be a key factor in many signaling pathways related to controlling cell survival, differentiation, and growth. The Grb2-SH2 domain has been a focus for the study of the interaction with peptides and small molecules to act as inhibitors in uncontrolled cell growth, and consequently inhibit tumor proliferation. Here we describe the almost complete assignment of the free SH2 domain at pH 7. This work prepares the ground for further structural studies, backbone dynamics, mapping of interactions and drug screening and development. TalosN secondary structure prediction showed great similarity with the available structures in the PDB.

摘要

生长因子受体结合蛋白2(Grb2)是一种由三个结构域组成的衔接蛋白,即N端SH3(nSH3)、SH2和C端SH3(cSH3)结构域。据报道,这种多结构域蛋白是许多与控制细胞存活、分化和生长相关信号通路中的关键因子。Grb2-SH2结构域一直是研究与肽和小分子相互作用以作为不受控制的细胞生长抑制剂从而抑制肿瘤增殖的焦点。在此,我们描述了pH 7条件下游离SH2结构域几乎完整的归属。这项工作为进一步的结构研究、主链动力学、相互作用图谱绘制以及药物筛选与开发奠定了基础。TalosN二级结构预测显示与蛋白质数据库(PDB)中现有的结构高度相似。

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