W20 Flashcards
What are the two major classes of macromolecules that comprise the ECM?
Proteoglycans and fibrous proteins
Name the four main fibrous proteins.
Collagens, elastin, laminin, and fibronectin
Describe the structure of fibrillar collagens.
Three polypeptides compose each procollagen molecule in a helical central domain with Gly-X(proline)-Y(hydroxyproline) repeats that form a left-handed helix. The three helices together form a right-handed super-helix. After secretion, proteases cleave off the N- and C-terminal globular domains to just leave the triple helix collagen that associates end-to-end to form collagen fibrils and cross-linked laterally via lysyl oxidase to form collagen fibres
What fibrillar collagens are found in the dermis and cartilage and tendons?
Collagen I in dermis, collagen II in cartilage and tendons
Name three disorders that are caused by collagen mutations.
Ehlers-Danlos syndrome, Osteogenesis imperfecta, and Epidermolysis bullosa
Explain the role of vitamin C in collagen synthesis.
Cofactor for proline hydroxylase and lysyl hydroxylase. Hydroxylated proline facilitates packing of collagen polypeptides into a trimer. Hydroxylated lysine generates covalent attachments between trimers
Explain the purpose of fibrillin.
Fibrillin is a large secreted protein that forms microfibrils that bind a number of ECM proteins. It binds elastin for assembly of elastic fibres, localises inactive TGF-beta complexes, and binds cell surfaces through integrin receptors
What disease is caused by mutation of fibrillin-1?
Marfan’s syndrome
Describe fibronectin.
Fibronectin dimers are crosslinked by transglutaminases to make fibronectin multimers. The tripeptide RGD motif found in the 10th repeated domain is key for cell binding
What two fibrous proteins are key components of the basement membrane?
Laminin and collagen IV
Describe the structure of laminin.
Composed of three polypeptides: alpha, beta, and gamma. Alpha has globular N- and C-termini, beta and gamma have globular N-termini and coiled-coil C-termini around the alpha chain
Describe the structure of collagen IV.
Globular domains are not removed by proteases hence form a different structure than collagen I, forming an extensive mesh network
Name the six cell-cell adhesions.
Tight junctions, adherens junctions, desmosomes, gap junctions, actin-linked cell-matrix junctions, and hemidesmosomes
What is the function of tight junctions?
Barrier function at the apical side of the epithelium, only allowing ions and small molecules to pass through, protective function to keep pathogens out
What proteins form tight junctions?
Claudin, and occludin
