dc.contributor.author | Xiong, S | |
dc.contributor.author | Lorenzen, K | |
dc.contributor.author | Couzens, AL | |
dc.contributor.author | Templeton, CM | |
dc.contributor.author | Rajendran, D | |
dc.contributor.author | Mao, DYL | |
dc.contributor.author | Juang, Y-C | |
dc.contributor.author | Chiovitti, D | |
dc.contributor.author | Kurinov, I | |
dc.contributor.author | Guettler, S | |
dc.contributor.author | Gingras, A-C | |
dc.contributor.author | Sicheri, F | |
dc.date.accessioned | 2018-06-08T08:07:09Z | |
dc.date.issued | 2018-08-07 | |
dc.identifier.citation | Structure (London, England : 1993), 2018, 26 (8), pp. 1101 - 1115.e6 | |
dc.identifier.issn | 0969-2126 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1755 | |
dc.identifier.eissn | 1878-4186 | |
dc.identifier.doi | 10.1016/j.str.2018.05.014 | |
dc.description.abstract | The human NDR family kinases control diverse aspects of cell growth, and are regulated through phosphorylation and association with scaffolds such as MOB1. Here, we report the crystal structure of the human NDR1 kinase domain in its non-phosphorylated state, revealing a fully resolved atypically long activation segment that blocks substrate binding and stabilizes a non-productive position of helix αC. Consistent with an auto-inhibitory function, mutations within the activation segment of NDR1 dramatically enhance in vitro kinase activity. Interestingly, NDR1 catalytic activity is further potentiated by MOB1 binding, suggesting that regulation through modulation of the activation segment and by MOB1 binding are mechanistically distinct. Lastly, deleting the auto-inhibitory activation segment of NDR1 causes a marked increase in the association with upstream Hippo pathway components and the Furry scaffold. These findings provide a point of departure for future efforts to explore the cellular functions and the mechanism of NDR1. | |
dc.format | Print-Electronic | |
dc.format.extent | 1101 - 1115.e6 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Epithelial Cells | |
dc.subject | Humans | |
dc.subject | Escherichia coli | |
dc.subject | Protein-Serine-Threonine Kinases | |
dc.subject | Hepatocyte Growth Factor | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Microtubule-Associated Proteins | |
dc.subject | Proto-Oncogene Proteins | |
dc.subject | Recombinant Proteins | |
dc.subject | Crystallography, X-Ray | |
dc.subject | Cloning, Molecular | |
dc.subject | Sequence Alignment | |
dc.subject | Signal Transduction | |
dc.subject | Gene Expression | |
dc.subject | Gene Expression Regulation | |
dc.subject | Binding Sites | |
dc.subject | Amino Acid Sequence | |
dc.subject | Protein Binding | |
dc.subject | Sequence Homology, Amino Acid | |
dc.subject | Substrate Specificity | |
dc.subject | Kinetics | |
dc.subject | Mutation | |
dc.subject | Genetic Vectors | |
dc.subject | Models, Molecular | |
dc.subject | Protein Interaction Domains and Motifs | |
dc.subject | HEK293 Cells | |
dc.subject | Protein Conformation, alpha-Helical | |
dc.subject | Protein Conformation, beta-Strand | |
dc.title | Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-05-17 | |
rioxxterms.versionofrecord | 10.1016/j.str.2018.05.014 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2018-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Structure (London, England : 1993) | |
pubs.issue | 8 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling | |
pubs.publication-status | Published | |
pubs.volume | 26 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Structural Biology of Cell Signalling | |
dc.contributor.icrauthor | Guettler, Sebastian | |