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Freitag, M.* ; Jaklin, S.* ; Padovani, F. ; Radzichevici, E. ; Zernia, S.* ; Schmoller, K.M. ; Stigler, J.*

Single-molecule experiments reveal the elbow as an essential folding guide in SMC coiled coil arms.

Biophys. J. 121, 4702-4713 (2022)
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Structural maintenance of chromosome (SMC) complexes form ring-like structures through exceptional elongated coiled coils (CC). Recent studies found that variable CC conformations including open and collapsed forms, which might result from discontinuities in the CC, facilitate the diverse functions of SMCs in DNA organization. However, a detailed description of the SMC CC architecture is still missing. Here, we study the structural composition and mechanical properties of SMC proteins with optical tweezers unfolding experiments using the isolated Psm3 CC as a model system. We find a comparatively unstable protein with three unzipping intermediates, which we could directly assign to CC features by crosslinking experiments and state-of-the-art prediction software. Particularly, the CC elbow is shown to be a flexible, potentially non-structured feature, which divides the CC into sections, induces a pairing shift from one CC strand to the other and could facilitate large-scale conformational changes - most likely via thermal fluctuations of the flanking CC sections. A replacement of the elbow amino acids hinders folding of the consecutive CC region and leads frequently to non-native misalignments, revealing the elbow as a guide for proper folding. Additional in vivo manipulation of the elbow flexibility resulted in impaired cohesin complexes, which directly links the sensitive CC architecture to the biological function of cohesin.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Fluctuation Theorem; Human Cohesin; Dna; Condensin; Proteins; Domains; Complex
ISSN (print) / ISBN 0006-3495
e-ISSN 1542-0086
Journal Biophysical Journal
Quellenangaben Volume: 121, Issue: 23, Pages: 4702-4713 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
Grants European Research Council (ERC)
ERC
DFG Emmy Noether grant
LMU Center for NanoScience CeNS