HDX-MS-optimized approach to characterize nanobodies as tools for biochemical and structural studies of class IB phosphoinositide 3-kinases
Manoj K. Rathinaswamy,Kaelin D. Fleming,Udit Dalwadi,Els Pardon,Noah J Harris,Calvin K. Yip,Jan Steyaert,John E. Burke,John E. Burke +8 more
TLDR
In this paper, the authors describe the characterization of multiple PI3Kγ binding single-chain camelid nanobodies using hydrogen-deuterium exchange (HDX) mass spectrometry (MS).About:
This article is published in Structure.The article was published on 2021-08-03 and is currently open access. It has received 7 citations till now. The article focuses on the topics: Lipid kinase activity & G protein-coupled receptor.read more
Citations
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Molecular basis for differential activation of p101 and p84 complexes of PI3Kγ by Ras and GPCRs
Manoj K. Rathinaswamy,Meredith L. Jenkins,Xuxiao Zhang,Jordan T B Stariha,Harish Ranga-prasad,Udit Dalwadi,Kaelin D. Fleming,Calvin K. Yip,Roger Williams,John E. Burke +9 more
TL;DR: Using a combination of X-ray crystallography, hydrogen deuterium exchange mass spectrometry (HDX-MS), electron microscopy, molecular modeling, single-molecule imaging, and activity assays, the authors identify molecular differences between PI3Kγ-p84 and p110γp101 that explain their differential membrane recruitment and activation by Ras and GPCRs.
Journal ArticleDOI
Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain
TL;DR: In this article , the authors defined the molecular basis for how an allosteric inhibitory nanobody potently inhibits kinase activity through rigidifying the helical domain and regulatory motif of the kinase domain.
Journal ArticleDOI
Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain
TL;DR: In this article , the authors defined the molecular basis for how an allosteric inhibitory nanobody potently inhibits kinase activity through rigidifying the helical domain and regulatory motif of the kinase domain.
Journal ArticleDOI
Open resources for chemical probes and their implications for future drug discovery
Esra Balıkçı,Kilian Huber +1 more
TL;DR: In this article , the authors summarize recent advances in chemical probe development for emerging target classes such as solute carriers and ubiquitin-related targets and highlight open resources to inform and facilitate chemical probe discovery.
Posted ContentDOI
Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain
Noah J Harris,Meredith L. Jenkins,Sung-Eun Nam,Manoj K. Rathinaswamy,M. A. Parson,Harish Ranga-prasad,Udit Dalwadi,Brandon E. Moeller,Eleanor Sheekey,Scott D. Hansen,Calvin K. Yip,John E. Burke +11 more
TL;DR: In this paper , the authors defined the molecular basis for how an allosteric inhibitory nanobody potently inhibits kinase activity through rigidifying the helical domain and regulatory motif of the kinase domain.
References
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The PRIDE database and related tools and resources in 2019: improving support for quantification data.
Yasset Perez-Riverol,Attila Csordas,Jingwen Bai,Manuel Bernal-Llinares,Suresh Hewapathirana,Deepti J. Kundu,Avinash Inuganti,Johannes Griss,Johannes Griss,Gerhard Mayer,Martin Eisenacher,Enrique Perez,Julian Uszkoreit,Julianus Pfeuffer,Timo Sachsenberg,Şule Yılmaz,Shivani Tiwary,Juergen Cox,Enrique Audain,Mathias Walzer,Andrew F. Jarnuczak,Tobias Ternent,Alvis Brazma,Juan Antonio Vizcaíno +23 more
TL;DR: Key statistics on the current data contents and volume of downloads are outlined, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas are outlined.
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cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination
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Naturally occurring antibodies devoid of light chains
Cécile Hamers-Casterman,Touriya Atarhouch,Serge Muyldermans,Gene E. Robinson,Hamers C,Songa Eb,Bendahman N,Raymond Hamers +7 more
TL;DR: The presence of considerable amounts of IgG-like material of Mr 100K in the serum of the camel, which is composed of heavy-chain dimers and devoid of light chains, but nevertheless have an extensive antigen-binding repertoire, opens new perspectives in the engineering of antibodies.
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Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Søren G. F. Rasmussen,Brian T. DeVree,Yaozhong Zou,Andrew C. Kruse,Ka Young Chung,Tong Sun Kobilka,Foon Sun Thian,Pil Seok Chae,Els Pardon,Els Pardon,Diane M. Calinski,Jesper Mosolff Mathiesen,Syed T. A. Shah,Joseph A. Lyons,Martin Caffrey,Samuel H. Gellman,Jan Steyaert,Jan Steyaert,Georgios Skiniotis,William I. Weis,Roger K. Sunahara,Brian K. Kobilka +21 more
TL;DR: This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR and the most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain.
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Discovery and saturation analysis of cancer genes across 21 tumour types
Michael S. Lawrence,Petar Stojanov,Craig H. Mermel,James T. Robinson,Levi A. Garraway,Todd R. Golub,Matthew Meyerson,Stacey Gabriel,Eric S. Lander,Gad Getz +9 more
TL;DR: It is found that large-scale genomic analysis can identify nearly all known cancer genes in these cancer types and 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis.
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