Chain Alignment of Collagen I Deciphered using Computationally Designed Heterotrimers
| Autor: | Katherine Stott, Samir W. Hamaia, Birgit Leitinger, Douglas R. Walker, Jeffrey D. Hartgerink, Douglas Sammon, Paul Brear, Richard W. Farndale, Abhishek A. Jalan, Emma Hunter |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
STRUCTURAL BASIS
Models Molecular Biochemistry & Molecular Biology Protein family VON-WILLEBRAND-FACTOR Protein Conformation DISCOIDIN DOMAIN RECEPTORS 0601 Biochemistry and Cell Biology Article Collagen Type I 03 medical and health sciences Protein structure Recognition sequence A3 DOMAIN Heterotrimeric G protein DDR2 Humans Amino Acid Sequence Amino Acids Molecular Biology Peptide sequence 030304 developmental biology 0303 health sciences Science & Technology TYROSINE KINASES IDENTIFICATION 0304 Medicinal and Biomolecular Chemistry Chemistry 030302 biochemistry & molecular biology RECOGNITION Computational Biology Cell Biology Cell biology AFFINITY BINDING Collagen Peptides Life Sciences & Biomedicine Discoidin domain Type I collagen Triple helix |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | The most abundant member of the collagen protein family, collagen I (also known as type I collagen; COL1), is composed of one unique (chain B) and two similar (chain A) polypeptides that self-assemble with one amino acid offset into a heterotrimeric triple helix. Given the offset, chain B can occupy either the leading (BAA), middle (ABA) or trailing (AAB) position of the triple helix, yielding three isomeric biomacromolecules with different protein recognition properties. Despite five decades of intensive research, there is no consensus on the position of chain B in COL1. Here, three triple-helical heterotrimers that each contain a putative von Willebrand factor (VWF) and discoidin domain receptor (DDR) recognition sequence from COL1 were designed with chain B permutated in all three positions. AAB demonstrated a strong preference for both VWF and DDR, and also induced higher levels of cellular DDR phosphorylation. Thus, we resolve this long-standing mystery and show that COL1 adopts an AAB register. |
| Databáze: | OpenAIRE |
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