The streptococcal collagen-binding protein CNE specifically interferes with {alpha}V{beta}3-mediated cellular interactions with triple helical collagen

• Collagen fibers expose distinct domains allowing for specific interactions with other extracellular matrix proteins and cells. To investigate putative collagen domains that govern integrin α(V)β(3)-mediated cellular interactions with native collagen fibers we took advantage of the streptococcal protein CNE that bound native fibrillar collagens. CNE specifically inhibited α(V)β(3)-dependent cell-mediated collagen gel contraction, PDGF BB-induced and α(V)β(3)-mediated adhesion of cells, and binding of fibronectin to native collagen. Using a Toolkit composed of overlapping, 27-residue triple helical segments of collagen type II, two CNE-binding sites present in peptides II-1 and II-44 were identified. These peptides lack the major binding site for collagen-binding β(1) integrins, defined by the peptide GFOGER. Peptide II-44 corresponds to a region of collagen known to bind collagenases, discoidin domain receptor 2, SPARC (osteonectin), and fibronectin. In addition to binding fibronectin, peptide II-44 but not II-1 inhibited α(V)β(3)-mediated collagen gel contraction and, when immobilized on plastic, supported adhesion of cells. Reduction of fibronectin expression by siRNA reduced PDGF BB-induced α(V)β(3)-mediated contraction. Reconstitution of collagen types I and II gels in the presence of CNE reduced collagen fibril diameters and fibril melting temperatures. Our data indicate that contraction proceeded through an indirect mechanism involving binding of cell-produced fibronectin to the collagen fibers. Furthermore, our data show that cell-mediated collagen gel contraction does not directly depend on the process of fibril formation.

Ämnesord

LANTBRUKSVETENSKAPER  -- Husdjursvetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Animal and Dairy Sience (hsv//eng)

LANTBRUKSVETENSKAPER  -- Veterinärmedicin (hsv//swe)

AGRICULTURAL SCIENCES  -- Veterinary Science (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)