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Direct Visualization of the Binding of Transforming Growth Factor Beta 1 with Cartilage Oligomeric Matrix Protein via High-Resolution Atomic Force Microscopy
- Source :
- The journal of physical chemistry. B, vol 124, iss 43, J Phys Chem B
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- This work reports the first direct observations of binding and complex formation between transforming growth factor beta 1 (TGF-β1) and cartilage oligomeric matrix protein (COMP) using high-resolution atomic force microscopy (AFM). Each COMP molecule consists of pentamers whose five identical monomeric units bundle at N-termini. From this central point, the five monomers’ flexible arms extend outward with C-terminal domains at the distal ends, forming a bouquet-like structure. In commonly used buffer solutions, TGF-β1 molecules typically form homodimers (majority), double dimers (minority), and aggregates (trace amount). Mixing of TGF-β1 and COMP leads to rapid binding and complex formation. The TGF-β1/COMP complexes contain one to three COMP and multiple TGF-β1 molecules. For complexes with one COMP, the structure is more compact and less flexible than that of COMP alone. For complexes with two or more COMP molecules, the conformation varies to a large degree from one complex to another. This is attributed to the presence of double dimers or aggregates of TGF-β1 molecules, whose size and multiple binding sites enable binding to more than one COMP. The number and location of individual TGF-β1 dimers are also clearly visible in all complexes. This molecular-level information provides new insight into the mechanism of chondrogenesis enhancement by TGF-β1/COMP complexes, i.e. simultaneous and multivalent presentation of growth factors. These presentations help explain the high efficacy in sustained activation of the signalling pathway to augment chondrogenesis.
- Subjects :
- musculoskeletal diseases
1.1 Normal biological development and functioning
Cartilage Oligomeric Matrix Protein
Microscopy, Atomic Force
010402 general chemistry
01 natural sciences
Article
Transforming Growth Factor beta1
chemistry.chemical_compound
Engineering
Underpinning research
0103 physical sciences
Materials Chemistry
Molecule
Physical and Theoretical Chemistry
Binding site
Cartilage oligomeric matrix protein
Microscopy
Binding Sites
010304 chemical physics
biology
Atomic force microscopy
Atomic Force
Transforming growth factor beta
Chondrogenesis
0104 chemical sciences
Surfaces, Coatings and Films
Monomer
chemistry
Physical Sciences
Chemical Sciences
biology.protein
Biophysics
Generic health relevance
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 15205207 and 15206106
- Volume :
- 124
- Database :
- OpenAIRE
- Journal :
- The Journal of Physical Chemistry B
- Accession number :
- edsair.doi.dedup.....f2ae04fb967a3622792abbb493f8ba12