Targeting the lateral interactions of transmembrane domain 5 of Epstein-Barr virus latent membrane protein 1

被引：14

作者：

Wang, Xiaohui ^{[1
,2
]}

Saludes, Jonel P. ^{[1
,2
]}

Zhao, Tina X. ^{[1
,2
]}

Csakai, Adam ^{[1
,2
]}

Fiorini, Zeno ^{[1
,2
]}

Chavez, Sherry A. ^{[1
,2
]}

Li, Jing ^{[3
]}

Lee, Gui-in ^{[4
]}

Varga, Krisztina ^{[5
]}

Yin, Hang ^{[1
,2
]}

机构：

[1] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA

[2] Univ Colorado, Biofrontiers Inst, Boulder, CO 80309 USA

[3] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rheumatol, Beijing 100032, Peoples R China

[4] Penn State Univ, Dept Chem, Abington, PA 19001 USA

[5] Univ Wyoming, Dept Chem, Laramie, WY 82071 USA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2012年 / 1818卷 / 09期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Epstein-Barr virus; Latent membrane protein 1; Transmembrane domain; Protein-protein interaction; High throughput screen; Small molecule inhibitor; CHEMICAL-SHIFT INDEX; SECONDARY STRUCTURE; SPECTROSCOPY; INHIBITORS; HELICES; DESIGN; AGENTS;

D O I：

10.1016/j.bbamem.2012.05.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The lateral transmembrane protein-protein interaction has been regarded as "undruggable" despite its importance in many biological processes. The homo-trimerization of transmembrane domain 5 (TMD-5) of latent membrane protein 1 (LMP-1) is critical for the constitutive oncogenic activation of the Epstein-Barr virus (EBV). Herein, we report a small molecule agent. NSC 259242 (compound 1), to be a TMD-5 self-association disruptor. Both the positively charged acetimidamide functional groups and the stilbene backbone of compound 1 are essential for its inhibitory activity. Furthermore, cell-based assays revealed that compound 1 inhibits full-length LMP-1 signaling in EBV infected B cells. These studies demonstrated a new strategy for identifying small molecule disruptors for investigating transmembrane protein-protein interactions. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：2282 / 2289

页数：8

共 22 条

[1] Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream [J].

Arkin, MR ;

Wells, JA .

NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) :301-317

[2]

Cavanagh J, 2007, PROTEIN NMR SPECTROSCOPY: PRINCIPLES AND PRACTICE, 2ND EDITION, P1

[3] NMRPIPE - A MULTIDIMENSIONAL SPECTRAL PROCESSING SYSTEM BASED ON UNIX PIPES [J].

DELAGLIO, F ;

GRZESIEK, S ;

VUISTER, GW ;

ZHU, G ;

PFEIFER, J ;

BAX, A .

JOURNAL OF BIOMOLECULAR NMR, 1995, 6 (03) :277-293

[4] Recognition of transmembrane helices by the endoplasmic reticulum translocon [J].

Hessa, T ;

Kim, H ;

Bihlmaier, K ;

Lundin, C ;

Boekel, J ;

Andersson, H ;

Nilsson, I ;

White, SH ;

von Heijne, G .

NATURE, 2005, 433 (7024) :377-381

[5] A Coiled-Coil Enabled Split-Luciferase Three-Hybrid System: Applied Toward Profiling Inhibitors of Protein Kinases [J].

Jester, Benjamin W. ;

Cox, Kurt J. ;

Gaj, Alicia ;

Shomin, Carolyn D. ;

Porter, Jason R. ;

Ghosh, Indraneel .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (33) :11727-11735

[6] Transmembrane Domain Oligomerization Propensity determined by ToxR Assay [J].

Joce, Catherine ;

Wiener, Alyssa ;

Yin, Hang .

JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2011, (51)

[7] Multi-Tox: Application of the ToxR-transcriptional reporter assay to the study of multi-pass protein transmembrane domain oligomerization [J].

Joce, Catherine ;

Wiener, Alyssa A. ;

Yin, Hang .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2011, 1808 (12) :2948-2953

[8] A structurally altered D,L-amino acid TCRα transmembrane peptide interacts with the TCRα and inhibits T-cell activation in vitro and in an animal model [J].

Quintana, Francisco J. ;

Gerber, Doron ;

Bloch, Itai ;

Cohen, Irun R. ;

Shai, Yechiel .

BIOCHEMISTRY, 2007, 46 (09) :2317-2325

[9] Detergent binding explains anomalous SDS-PAGE migration of membrane proteins [J].

Rath, Arianna ;

Glibowicka, Mira ;

Nadeau, Vincent G. ;

Chen, Gong ;

Deber, Charles M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (06) :1760-1765

[10] Amyloid beta 42 peptide (Aβ42)-lowering compounds directly bind to Aβ and interfere with amyloid precursor protein (APP) transmembrane dimerization [J].

Richter, Luise ;

Munter, Lisa-Marie ;

Ness, Julia ;

Hildebrand, Peter W. ;

Dasari, Muralidhar ;

Unterreitmeier, Stephanie ;

Bulic, Bruno ;

Beyermann, Michael ;

Gust, Ronald ;

Reif, Bernd ;

Weggen, Sascha ;

Langosch, Dieter ;

Multhaup, Gerd .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (33) :14597-14602

← 1 2 3 →