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A "spindle and thread" mechanism unblocks p53 translation by modulating N-terminal disorder

M. Kaldmäe, T. Vosselman, X. Zhong, D. Lama, G. Chen, M. Saluri, N. Kronqvist, JW. Siau, AS. Ng, FJ. Ghadessy, P. Sabatier, B. Vojtesek, M. Sarr, C. Sahin, N. Österlund, LL. Ilag, VA. Väänänen, S. Sedimbi, M. Arsenian-Henriksson, RA. Zubarev, L....

. 2022 ; 30 (5) : 733-742.e7. [pub] 20220314

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22018468
E-zdroje Online Plný text

NLK Cell Press Free Archives od 1995-01-01 do Před 1 rokem
Free Medical Journals od 1995 do Před 1 rokem
Free Medical Journals od 1995 do Před 1 rokem

Odkazy

PubMed 35290795
DOI 10.1016/j.str.2022.02.013
Knihovny.cz E-zdroje

Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of "life on the edge of solubility." Here, we investigate whether these features can be modulated by fusing the protein to a highly soluble spider silk domain (NT∗). The chimeric protein displays highly efficient translation and is fully active in human cancer cells. Biophysical characterization reveals a compact conformation, with the disordered transactivation domain of p53 wrapped around the NT∗ domain. We conclude that interactions with NT∗ help to unblock translation of the proline-rich disordered region of p53. Expression of partially disordered cancer targets is similarly enhanced by NT∗. In summary, we demonstrate that inducing co-translational folding via a molecular "spindle and thread" mechanism unblocks protein translation in vitro.

Citace poskytuje Crossref.org

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$a Vosselman, Thibault $u Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet - Biomedicum, Solnavägen 9, 17165 Solna, Sweden
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$a Zhong, Xueying $u Department of Biomedical Engineering and Health Systems, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), KTH Royal Institute of Technology, 141 83 Huddinge, Sweden
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$a Kronqvist, Nina $u Department of Biosciences and Nutrition, Karolinska Institutet, 148 13 Huddinge, Sweden
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