6BXI

X-ray crystal structure of NDR1 kinase domain

Summary for 6BXI

• Entry DOI: 10.2210/pdb6bxi/pdb
• Descriptor: Serine/threonine-protein kinase 38, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: kinase fold with atypically long activation segment, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 78567.93

Authors

Xiong, S.,Sicheri, F. (deposition date: 2017-12-18, release date: 2018-08-29, Last modification date: 2024-03-13)

Primary citation

Xiong, S.,Lorenzen, K.,Couzens, A.L.,Templeton, C.M.,Rajendran, D.,Mao, D.Y.L.,Juang, Y.C.,Chiovitti, D.,Kurinov, I.,Guettler, S.,Gingras, A.C.,Sicheri, F.
Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment.
Structure, 26:1101-1115.e6, 2018

PubMed 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.

PubMed: 29983373
DOI: 10.1016/j.str.2018.05.014

Experimental method

X-RAY DIFFRACTION (2.2 Å)