Open Access
,
volume 119
,
issue 38
Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα
Jonathan R Hart
1
,
Xiao Liu
2, 3
,
Chen Pan
4
,
Anyi Liang
5
,
Lynn Ueno
1
,
Yingna Xu
6
,
Alexandra Quezada
1
,
Xinyu Zou
5
,
Su Yang
1
,
Qing Tong Zhou
6
,
Steve Schoonooghe
7
,
Gholamreza Hassanzadeh-Ghassabeh
7
,
Tian Xia
5
,
Wenqing Shui
4
,
De-Hua Yang
2, 3
,
Peter K. Vogt
1
,
Ming-Wei Wang
6, 8, 9
7
8
Research Center for Deepsea Bioresources, Sanya 572025, China
|
Publication type: Journal Article
Publication date: 2022-09-12
scimago Q1
wos Q1
SJR: 3.414
CiteScore: 16.5
Impact factor: 9.1
ISSN: 00278424, 10916490
PubMed ID:
36095215
Multidisciplinary
Abstract
Nanobodies and chemical cross-linking were used to gain information on the identity and positions of flexible domains of PI3Kα. The application of chemical cross-linking mass spectrometry (CXMS) facilitated the identification of the p85 domains BH, cSH2, and SH3 as well as their docking positions on the PI3Kα catalytic core. Binding of individual nanobodies to PI3Kα induced activation or inhibition of enzyme activity and caused conformational changes that could be correlated with enzyme function. Binding of nanobody Nb3-126 to the BH domain of p85α substantially improved resolution for parts of the PI3Kα complex, and binding of nanobody Nb3-159 induced a conformation of PI3Kα that is distinct from known PI3Kα structures. The analysis of CXMS data also provided mechanistic insights into the molecular underpinning of the flexibility of PI3Kα.
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Total citations:
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Citations from 2024:
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(46.67%)
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GOST
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Hart J. R. et al. Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα // Proceedings of the National Academy of Sciences of the United States of America. 2022. Vol. 119. No. 38.
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Hart J. R., Liu X., Pan C., Liang A., Ueno L., Xu Y., Quezada A., Zou X., Yang S., Zhou Q. T., Schoonooghe S., Hassanzadeh-Ghassabeh G., Xia T., Shui W., Yang D., Vogt P. K., Wang M. Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα // Proceedings of the National Academy of Sciences of the United States of America. 2022. Vol. 119. No. 38.
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RIS
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TY - JOUR
DO - 10.1073/pnas.2210769119
UR - https://doi.org/10.1073/pnas.2210769119
TI - Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα
T2 - Proceedings of the National Academy of Sciences of the United States of America
AU - Hart, Jonathan R
AU - Liu, Xiao
AU - Pan, Chen
AU - Liang, Anyi
AU - Ueno, Lynn
AU - Xu, Yingna
AU - Quezada, Alexandra
AU - Zou, Xinyu
AU - Yang, Su
AU - Zhou, Qing Tong
AU - Schoonooghe, Steve
AU - Hassanzadeh-Ghassabeh, Gholamreza
AU - Xia, Tian
AU - Shui, Wenqing
AU - Yang, De-Hua
AU - Vogt, Peter K.
AU - Wang, Ming-Wei
PY - 2022
DA - 2022/09/12
PB - Proceedings of the National Academy of Sciences (PNAS)
IS - 38
VL - 119
PMID - 36095215
SN - 0027-8424
SN - 1091-6490
ER -
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BibTex (up to 50 authors)
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@article{2022_Hart,
author = {Jonathan R Hart and Xiao Liu and Chen Pan and Anyi Liang and Lynn Ueno and Yingna Xu and Alexandra Quezada and Xinyu Zou and Su Yang and Qing Tong Zhou and Steve Schoonooghe and Gholamreza Hassanzadeh-Ghassabeh and Tian Xia and Wenqing Shui and De-Hua Yang and Peter K. Vogt and Ming-Wei Wang},
title = {Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2022},
volume = {119},
publisher = {Proceedings of the National Academy of Sciences (PNAS)},
month = {sep},
url = {https://doi.org/10.1073/pnas.2210769119},
number = {38},
doi = {10.1073/pnas.2210769119}
}