Structural and functional analysis of two small leucine-rich repeat proteoglycans, fibromodulin and chondroadherin. 2017

Patricia Paracuellos, and Sebastian Kalamajski, and Arkadiusz Bonna, and Dominique Bihan, and Richard W Farndale, and Erhard Hohenester
Department of Life Sciences, Imperial College London, London, United Kingdom.

The small leucine-rich proteoglycans (SLRPs) are important regulators of extracellular matrix assembly and cell signalling. We have determined crystal structures at ~2.2Å resolution of human fibromodulin and chondroadherin, two collagen-binding SLRPs. Their overall fold is similar to that of the prototypical SLRP, decorin, but unlike decorin neither fibromodulin nor chondroadherin forms a stable dimer. A previously identified binding site for integrin α2β1 maps to an α-helix in the C-terminal cap region of chondroadherin. Interrogation of the Collagen Toolkits revealed a unique binding site for chondroadherin in collagen II, and no binding to collagen III. A triple-helical peptide containing the sequence GAOGPSGFQGLOGPOGPO (O is hydroxyproline) forms a stable complex with chondroadherin in solution. In fibrillar collagen I and II, this sequence is aligned with the collagen cross-linking site KGHR, suggesting a role for chondroadherin in cross-linking.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D003553 Cystine A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Copper Cystinate,L-Cystine,L Cystine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071235 Fibromodulin A small leucine-rich proteoglycan that contains 4 KERATAN SULFATE chains within the leucine repeat region. It interacts with COLLAGEN TYPE I and COLLAGEN TYPE II fibrils and may function to control the rate of EXTRACELLULAR MATRIX assembly. It also sequesters TRANSFORMING GROWTH FACTOR BETA in the extracellular matrix. FMOD Protein
D000072757 Protein Conformation, beta-Strand A secondary structure of proteins where the amino (N-H) groups of a polypeptide backbone, three to ten amino acids in length, establish hydrogen bonds with the carbonyl (C Protein Conformation, beta-Sheet,beta-Pleated Sheet,beta-Sheet,beta-Sheets,beta-Strand,beta-Stranded Structures,beta-Strands,Conformation, beta-Sheet Protein,Conformation, beta-Strand Protein,Conformations, beta-Sheet Protein,Conformations, beta-Strand Protein,Protein Conformation, beta Sheet,Protein Conformation, beta Strand,Protein Conformations, beta-Sheet,Protein Conformations, beta-Strand,Sheet, beta-Pleated,Sheets, beta-Pleated,beta Pleated Sheet,beta Sheet,beta Sheets,beta Strand,beta Stranded Structures,beta Strands,beta-Pleated Sheets,beta-Sheet Protein Conformation,beta-Sheet Protein Conformations,beta-Strand Protein Conformation,beta-Strand Protein Conformations,beta-Stranded Structure
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D012996 Solutions The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed) Solution
D016326 Extracellular Matrix Proteins Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ). Extracellular Matrix Protein,Matrix Protein, Extracellular,Matrix Proteins, Extracellular,Protein, Extracellular Matrix,Proteins, Extracellular Matrix
D054730 Protein Interaction Domains and Motifs Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS. Protein Interaction Domains,Protein Interaction Motifs,Binding Motifs, Protein Interaction,Protein Interaction Binding Motifs,Protein-Protein Interaction Domains,Domain, Protein Interaction,Domain, Protein-Protein Interaction,Domains, Protein Interaction,Domains, Protein-Protein Interaction,Motif, Protein Interaction,Motifs, Protein Interaction,Protein Interaction Domain,Protein Interaction Motif,Protein Protein Interaction Domains,Protein-Protein Interaction Domain

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