Protein-induced photophysical changes to the amyloid indicator dye thioflavin T

硫黄素 荧光团 化学 量子产额 荧光 单体 淀粉样蛋白(真菌学) 生物物理学 光化学 阿尔茨海默病 生物 有机化学 医学 物理 疾病 病理 量子力学 聚合物 无机化学
作者
Leslie S. Wolfe,Matthew F. Calabrese,Abhinav Nath,Dorottya Blaho,Andrew D. Miranker,Yong Xiong
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [National Academy of Sciences]
卷期号:107 (39): 16863-16868 被引量:306
标识
DOI:10.1073/pnas.1002867107
摘要

The small molecule thioflavin T (ThT) is a defining probe for the identification and mechanistic study of amyloid fiber formation. As such, ThT is fundamental to investigations of serious diseases such as Alzheimer’s disease, Parkinson disease, and type II diabetes. For each disease, a different protein undergoes conformational conversion to a β-sheet rich fiber. The fluorescence of ThT exhibits an increase in quantum yield upon binding these fibers. Despite its widespread use, the structural basis for binding specificity and for the changes to the photophysical properties of ThT remain poorly understood. Here, we report the co-crystal structures of ThT with two alternative states of β-2 microglobulin (β2m); one monomeric, the other an amyloid-like oligomer. In the latter, the dye intercalates between β-sheets orthogonal to the β-strands. Importantly, the fluorophore is bound in such a manner that a photophysically relevant torsion is limited to a range of angles generally associated with low, not high, quantum yield. Quantum mechanical assessment of the fluorophore shows the electronic distribution to be strongly stabilized by aromatic interactions with the protein. Monomeric β2m gives little increase in ThT fluorescence despite showing three fluorophores, at two binding sites, in configurations generally associated with high quantum yield. Our efforts fundamentally extend existing understanding about the origins of amyloid-induced photophysical changes. Specifically, the β-sheet interface that characterizes amyloid acts both sterically and electronically to stabilize the fluorophore’s ground state electronic distribution. By preventing the fluorophore from adopting its preferred excited state configuration, nonradiative relaxation pathways are minimized and quantum yield is increased.

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
dududu发布了新的文献求助10
2秒前
阳光海蓝完成签到,获得积分10
3秒前
简单平蓝发布了新的文献求助10
3秒前
科目三应助认真的汉堡采纳,获得10
3秒前
mmll完成签到,获得积分20
8秒前
简单的如曼完成签到 ,获得积分10
9秒前
12秒前
mmll发布了新的文献求助10
13秒前
14秒前
科研通AI2S应助刘小明采纳,获得10
18秒前
slin_sjtu发布了新的文献求助10
18秒前
18秒前
小元发布了新的文献求助10
18秒前
CYY发布了新的文献求助10
19秒前
充电宝应助科研通管家采纳,获得10
23秒前
天天快乐应助科研通管家采纳,获得10
23秒前
今后应助科研通管家采纳,获得10
23秒前
脑洞疼应助科研通管家采纳,获得10
23秒前
完美世界应助科研通管家采纳,获得10
23秒前
无花果应助科研通管家采纳,获得10
23秒前
小蘑菇应助科研通管家采纳,获得10
23秒前
23秒前
共享精神应助阳光海蓝采纳,获得10
24秒前
HEAR应助风趣钻石采纳,获得10
27秒前
千日粉完成签到 ,获得积分10
27秒前
一步一个脚印完成签到,获得积分10
28秒前
动漫大师发布了新的文献求助20
28秒前
令狐秋尽发布了新的文献求助10
28秒前
什么也难不倒我完成签到 ,获得积分10
29秒前
科研通AI5应助qcx采纳,获得30
32秒前
32秒前
听闻墨笙完成签到 ,获得积分10
33秒前
35秒前
科研通AI5应助Nhiii采纳,获得10
36秒前
CipherSage应助简单的如曼采纳,获得10
38秒前
1851611453完成签到 ,获得积分10
39秒前
41秒前
41秒前
甘sir完成签到 ,获得积分10
42秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
Continuum Thermodynamics and Material Modelling 2000
Encyclopedia of Geology (2nd Edition) 2000
105th Edition CRC Handbook of Chemistry and Physics 1600
Maneuvering of a Damaged Navy Combatant 650
Периодизация спортивной тренировки. Общая теория и её практическое применение 310
Mixing the elements of mass customisation 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3778363
求助须知:如何正确求助?哪些是违规求助? 3324059
关于积分的说明 10216978
捐赠科研通 3039300
什么是DOI,文献DOI怎么找? 1667944
邀请新用户注册赠送积分活动 798438
科研通“疑难数据库(出版商)”最低求助积分说明 758385