Journal Article

FZJ-2026-02193

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Calmodulin assists during co‐translational folding of the K V 7 .2 channel calcium responsive domain

Muguruza-Montero, A. (Corresponding author) ; Tait, J. R. ; M-Alicante, S. ; Metola, A. ; Nuñez, E. ; Urrutia, J. ; Sunderlíková, V. ; Katranidis, A. ; von Heijne, G. ; Tans, S. J. ; Villarroel, A. (Corresponding author)

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/pro.70552  doi:10.34734/FZJ-2026-02193

Abstract: In vivo, the majority of nascent protein chains must begin folding during translation in order to obtain their native structure. While the importance of co-translational folding has become increasingly clear, the specific mechanisms underlying the coordination between the ribosome, nascent chain and molecular chaperones are still uncertain. Here, we have constructed a model of the co-translational folding pathway of the calcium responsive domain (CRD) of the human neuronal KV7.2 human neuronal ion channel, showing that calmodulin (CaM) is crucial. By combining Force Profile Analysis and single-molecule force spectroscopy techniques, we found that CaM, in a calcium-dependent manner, affects early folding events involving three key α-helices in the CRD. In addition, this study suggests that CaM at early stages induces the formation of metastable hairpins, as a part of the co-translational folding pathway. These findings expand on the role of CaM as a key regulator of folding in eukaryotes: not only as an essential cellular signaling protein, but also as a bona fide co-translational molecular chaperone.

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Contributing Institute(s):

1. Strukturbiologie (ER-C-3)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
2. 5352 - Understanding the Functionality of Soft Matter and Biomolecular Systems (POF4-535) (POF4-535)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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