一种高亲和力人工肽对全长HIV-1 Nef与Hck SH3结构域的竞争性置换

Competitive displacement of full-length HIV-1 Nef from the Hck SH3 domain by a high-affinity artificial peptide.

作者信息

Stangler Thomas, Tran Tuyen, Hoffmann Silke, Schmidt Holger, Jonas Esther, Willbold Dieter

机构信息

Institut für Physikalische Biologie and BMFZ, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.

出版信息

Biol Chem. 2007 Jun;388(6):611-5. doi: 10.1515/BC.2007.075.

DOI:10.1515/BC.2007.075

PMID:17552908

Abstract

We studied the interaction of the artificial 12-aa proline-rich peptide PD1 with the SH3 domain of the hematopoietic cell kinase Hck and the peptide's potency in competitively displacing HIV-1 Nef from the Hck SH3 domain. PD1 was obtained from a phage display screen and exhibits exceptional affinity for the Hck SH3 domain (K(d)=0.23 microM). Competition experiments using NMR spectroscopy demonstrate that the peptide even displaces Nef from Hck SH3 and allow for estimation of the Nef-Hck SH3 dissociation constant (K(d)=0.44 microM), the strongest SH3 ligand interaction known so far. Consequences of this study for novel antiviral concepts are discussed.

摘要

我们研究了人工合成的富含脯氨酸的12氨基酸肽PD1与造血细胞激酶Hck的SH3结构域之间的相互作用，以及该肽在竞争性地将HIV-1 Nef从Hck SH3结构域中置换出来方面的效力。PD1是从噬菌体展示筛选中获得的，对Hck SH3结构域表现出非凡的亲和力（解离常数K(d)=0.23微摩尔）。使用核磁共振光谱的竞争实验表明，该肽甚至能将Nef从Hck SH3结构域中置换出来，并能估算出Nef-Hck SH3的解离常数（K(d)=0.44微摩尔），这是迄今为止已知的最强的SH3配体相互作用。本文讨论了该研究对新型抗病毒概念的意义。