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Meier, S.* ; Bohnacker, S. ; Klose, C.J.* ; Lopez, A. ; Choe, C.A.* ; Schmid, P.W.N.* ; Bloemeke, N.* ; Rührnößl, F.* ; Haslbeck, M.* ; Esser-von Bieren, J.* ; Sattler, M. ; Huang, P.S.* ; Feige, M.J.*

The molecular basis of chaperone-mediated interleukin 23 assembly control.

Nat. Commun. 10:4121 (2019)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
The functionality of most secreted proteins depends on their assembly into a defined quaternary structure. Despite this, it remains unclear how cells discriminate unassembled proteins en route to the native state from misfolded ones that need to be degraded. Here we show how chaperones can regulate and control assembly of heterodimeric proteins, using interleukin 23 (IL-23) as a model. We find that the IL-23 α-subunit remains partially unstructured until assembly with its β-subunit occurs and identify a major site of incomplete folding. Incomplete folding is recognized by different chaperones along the secretory pathway, realizing reliable assembly control by sequential checkpoints. Structural optimization of the chaperone recognition site allows it to bypass quality control checkpoints and provides a secretion-competent IL-23α subunit, which can still form functional heterodimeric IL-23. Thus, locally-restricted incomplete folding within single-domain proteins can be used to regulate and control their assembly.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 4121 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed