Deciphering the folding code of collagens
Malcor, Jean-Daniel (CNRS UMR 5305 University of Lyon. Laboratory of Tissue Biology and Therapeutic Engineering)
Ferruz, Noelia (Present Address: Centre for Genomic Regulation)
Romero-Romero, Sergio (Universidad Nacional Autónoma de México. Present Address: Department of Biochemistry and Structural Biology. Instituto de Fisiología Celular)
Dhingra, Surbhi (University of Bayreuth. Department of Biochemistry)
Sagar, Vamika (University of Bayreuth. Department of Biomaterials)
Jalan, Abhishek A. (University of Bayreuth. Department of Biomaterials)

Data:	2025
Resum:	Collagen proteins contain a characteristic structural motif called a triple helix. During the self-assembly of this motif, three polypeptides form a folding nucleus at the C-termini and then propagate towards the N-termini like a zip-chain. While polypeptides from human collagens contain up to a 1000 amino acids, those found in bacteria can contain up to 6000 amino acids. Additionally, the collagen polypeptides are also frequently interrupted by non-helical sequences that disrupt folding and reduce stability. Given the length of polypeptides and the disruptive interruptions, compensating mechanisms that stabilize against local unfolding during propagation and offset the entropic cost of folding are not fully understood. Here, we show that the information for the correct folding of collagen triple helices is encoded in their sequence as interchain electrostatic interactions, which likely act as molecular clamps that prevent local unfolding. In the case of humans, disrupting these electrostatic interactions is associated with severe to lethal diseases. Collagen triple helices are found in all the three domains of life as well as viruses. Here, the authors show that collagens have converged on a similar folding mechanism that employs salt bridge interactions to guide the triple helix assembly.
Ajuts:	Royal Society AL 221042 Agence Nationale de la Recherche (French National Research Agency) CARTEGRIN ANR21-CE19-0017 Alexander von Humboldt-Stiftung (Alexander von Humboldt Foundation) Not available EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)) 647548
Drets:	Aquesta url de drets no existeix a la base de dades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Protein folding ; Biophysics ; Proteins
Publicat a:	Nature communications, Vol. 16 (March 2025), art. 2702, ISSN 2041-1723

DOI: 10.1038/s41467-024-54046-y
PMID: 40108160

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