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Epitope analysis of the complex of CD73 and HB0039 by HDX-MS

ABSTRACT: To identify the epitope of the anti-CD73 antibody HB0039 on CD73 antigen

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

DISEASE(S): Breast Cancer

SUBMITTER: Jingen Xu

LAB HEAD: Jingen Xu

PROVIDER: PXD057868 | Pride | 2025-05-07

REPOSITORIES: Pride

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			Action	DRS
	Ab2_Ag_10_20200805_184853.raw	Raw
	Ab2_Ag_10_20200805_190338.raw	Raw
	Ab2_Ag_10_20200805_191824.raw	Raw
	Ab2_Ag_300_20200805_202428.raw	Raw
	Ab2_Ag_300_20200805_204402.raw	Raw

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Publications

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

Xu Jin-Gen JG Chen Shi S He Yang Y Zhu Xi X Wang Yanting Y Ye Zhifeng Z Zhou Jin Chuan JC Wu Xuanhui X Zhang Lei L Ren Xiaochen X Jia Huifeng H Yu Haijia H Wei Xiaoyue X Feng Yujie Y Chen Xiaofang X Cui Xiaopei X Pan Xianfei X Wang Shaojie S Xia Simin S Shang Hongjie H Pu Yueqing Y Xu Wei W Li Haidong H Chen Qian Q Chen Zeyu Z Wang Manfu M Yan Xiaodong X Shi Hui H Li Mingwei M Xia Yisui Y Bellelli Roberto R Dong Shunli S He Jun J Huang Jun J Cai Chen-Leng CL Zhu Xiangyang X Zhan Yifan Y Wan Li L

Nature communications 20241230 1

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045. HB0045 is a 1:1 mixture of two humanized monoclonal IgG1 antibodies (mAbs), HB0038 and HB0039. The cocktail not only harnesses the advantages of its parental mAbs in enzyme inhibition but a ...[more]

PMID: 39738003

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Epitope analysis of the complex of CD73 and HB0038 by HDX-MS

Project description:Epitope analysis of the complex of CD73 antigen and the anti-CD73 antibody HB0038 by HDX-MS

2025-05-07 | PXD057867 | Pride

Prion-like low complexity regions enable avid virus-host interactions during HIV-1 infection

Project description:Cellular proteins CPSF6, NUP153 and SEC24C play crucial roles in HIV-1 infection. While weak interactions of short FG peptides to isolated capsid hexamers have been characterized, how these proteins engage biologically relevant extended HIV-1 capsid lattices is unknown. We have identified that prion-like low complexity regions (LCR) enable avid binding of CPSF6, NUP153 and SEC24C to curved hexameric capsid lattices. Structural studies reveal that LCR-LCR interactions mediate multivalent CPSF6 assembly, which are templated by binding of CPSF6 FG peptides to a subset of hydrophobic capsid pockets positioned along adjoining hexamers. CPSF6 LCR mediated avid binding to HIV-1 cores is essential for functional virus-host interactions in infected cells. Investigational drug lenacapavir can access unoccupied hydrophobic pockets in the CPSF6-HIV-1 complex and potently impair HIV-1 inside the nucleus without displacing the tightly bound cellular cofactor from virus cores. These results elucidate previously undescribed mechanisms of virus-host interactions and potent inhibition of HIV-1.

2022-08-31 | PXD030332 | Pride

Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro (HDX-MS continuous labeling)

Project description:SARS-CoV-2, a human coronavirus, is the causative agent of the COVID-19 pandemic, entailing enormous disruption worldwide. Its ~30 kb RNA genome is translated into two large polyproteins subsequently cleaved by viral papain-like protease and main protease (Mpro/nsp5). Polyprotein processing is essential yet incompletely understood. We studied Mpro-mediated processing of the nsp7-10/11 polyprotein, whose mature products are cofactors of the viral replicase, identifying the order of cleavages: 1) nsp9-10, 2) nsp8-9/nsp10-11, and 3) nsp7-8. Integrative modeling based on mass spectrometry (including hydrogen-deuterium exchange and cross-linking) and X-ray scattering yielded three-dimensional models of the nsp7-10/11 polyprotein, and the data suggest that the nsp7-10/11 structure in complex with Mpro strongly resembles the unbound polyprotein. Our array of techniques supports the notion that interplay between polyprotein conformation and junction accessibility determine the preference and order of cleavages. Finally, we leveraged assays of limited proteolysis by Mpro of nsp7-11 using a series of inhibitors/binders to characterize Mpro inhibition using a polyprotein substrate.

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Selective modulation of nuclear receptor LRH-1 through target-ing buried and surface regions of the binding pocket

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2022-05-04 | PXD031099 | Pride

HDX-MS Analysis of RORg:RORE:SRC3 Complexes

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Hydrogen Deuterium Exchange of the CERT1 protein

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Structural proteomics defines a sequential priming mechanism for the progesterone receptor (HDX-MS)

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2025-04-07 | PXD056400 | Pride

Structure of the phosphoinositide 3-kinase p110-p101 complex reveals molecular mechanism of GPCR activation

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