Collagen’s primary structure determines collagen:HSP47 complex stoichiometry
| Autor: | Philipp W. N. Schmid, Matthias Mörgelin, Jan M. Gebauer, Sinan Oecal, Ulrich Baumann, Johannes Buchner, Elena Theres Abraham |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
collagen
SPARC secreted protein acidic and rich in cysteine (also known as BM-40 or osteonectin) Models Molecular crystal structure COMP cartilage oligomeric matrix protein Protein Conformation Collagen helix COL1A2 collagen type I alpha 2 chain Protein Data Bank (RCSB PDB) Crystallography X-Ray Biochemistry Protein–protein interaction extracellular matrix proteins ER endoplasmic reticulum COPII coat protein complex II Dogs Animals Amino Acid Sequence Binding site DDR2 discoidin domain-containing receptor 2 PDB protein data bank Molecular Biology CMP collagen model peptide HSP47 Heat-Shock Proteins chemistry.chemical_classification COL5A2 collagen type V alpha 2 chain AUC analytical ultracentrifugation Binding Sites biology PEDF pigment epithelium-derived factor Protein primary structure COL2A1 collagen type II alpha 1 chain Cell Biology Amino acid stoichiometry Folding (chemistry) HSP47 heat shock protein 47 protein–protein interaction COL1A1 collagen type I alpha 1 chain chemistry Chaperone (protein) biology.protein Biophysics TANGO1 transport and Golgi organization 1 Peptides Research Article Protein Binding |
| Zdroj: | The Journal of Biological Chemistry 'Journal of Biological Chemistry ', vol: 297, pages: 101169-1-101169-13 (2021) |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Collagens play important roles in development and homeostasis in most higher organisms. In order to function, collagens require the specific chaperone HSP47 for proper folding and secretion. HSP47 is known to bind to the collagen triple-helix but the exact positions and numbers of binding sites are not clear. Here, we employed a collagen II peptide library to characterize high-affinity binding sites for HSP47. We show that many previously predicted binding sites have very low affinities due to the presence of a negatively charged amino acid in the binding motif. In contrast, large hydrophobic amino acids like phenylalanine at certain positions in the collagen sequence increase binding strength. For further characterization, we determined two crystal structures of HSP47 bound to peptides containing phenylalanine or leucine. These structures deviate significantly from previously published ones in which different collagen sequences were used. They reveal local conformational rearrangements of HSP47 at the binding site to accommodate the large hydrophobic side chain from the middle strand of the collagen triple helix and, most surprisingly, possess an altered binding stoichiometry in form of a 1:1 complex. This altered stoichiometry is explained by steric collisions with the second HSP47 molecule present in all structures determined thus far caused by the newly introduced large hydrophobic residue placed on the trailing strand. This exemplifies the importance of considering all three sites of homotrimeric collagen as independent interaction surfaces and may provide insight into the formation of higher oligomeric complexes at promiscuous collagen binding sites. |
| Databáze: | OpenAIRE |
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