8DD4

PI 3-kinase alpha with nanobody 3-142

Summary for 8DD4

• Entry DOI: 10.2210/pdb8dd4/pdb
• EMDB information: 27334
• Descriptor: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, Phosphatidylinositol 3-kinase regulatory subunit alpha (3 entities in total)
• Functional Keywords: phosphoinositide 3-kinase (pi3k), activation, inhibition, nanobody, conformational changes, structural protein, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 211445.78

Authors

Hart, J.R.,Liu, X.,Pan, C.,Liang, A.,Ueno, L.,Xu, Y.,Quezada, A.,Zou, X.,Yang, S.,Zhou, Q.,Schoonooghe, S.,Hassanzadeh-Ghassabeh, G.,Xia, T.,Shui, W.,Yang, D.,Vogt, P.K.,Wang, M.-W. (deposition date: 2022-06-17, release date: 2022-09-21, Last modification date: 2024-06-12)

Primary citation

Hart, J.R.,Liu, X.,Pan, C.,Liang, A.,Ueno, L.,Xu, Y.,Quezada, A.,Zou, X.,Yang, S.,Zhou, Q.,Schoonooghe, S.,Hassanzadeh-Ghassabeh, G.,Xia, T.,Shui, W.,Yang, D.,Vogt, P.K.,Wang, M.W.
Nanobodies and chemical cross-links advance the structural and functional analysis of PI3K alpha.
Proc.Natl.Acad.Sci.USA, 119:e2210769119-e2210769119, 2022

PubMed 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.

PubMed: 36095215
DOI: 10.1073/pnas.2210769119

Experimental method

ELECTRON MICROSCOPY (3.1 Å)