http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Characterization of the interactions between collagen and collagen-binding integrins
viii, 111 leaves : illustrations ; 28 cm.
ABSTRACT: Collagen is the most abundant extracellular matrix molecule, which plays an important role in maintaining the structure of various tissues. In addition, collagen is also involved in cell signaling by interacting with cells. The direct collagen-cell interactions are mediated by cell surface receptors and the major collagen-binding receptors belong to the integrin family. To understand the important biological processes that involve collagen-cell communication, such as organogenesis and tissue remodeling, it is essential that we know the mechanistic detail of the interaction between integrins and collagen. My goal was identifying the integrin-binding motifs on collagens, the first step in this interaction. There are four collagen-binding integrins, α₁β₁, α₂β₁, α₁₀β₁, and α₁₁β₁, known so far. Their collagen binding domain, called I domain, is located in the α subunit. In my studies, I have used the recombinant I domains from integrins α₁ and α₂ (α₁I and α₂I). There had been only two collagen motifs, GFOGER (O:hydoxyproline) and GLOGER, identified as integrin-binding collagen sequences, however, those are not found in all collagen, for example not in type III collagen. Using rotary shadowing followed by electron microscopy, we located the binding site for α₁I and α₂I in type III collagen and identified a novel high affinity binding motif, GROGER. Interestingly, collagen-like proteins are also found in bacteria. We studied the interaction between Streptococcal collagen-like proteins (Scl) proteins and collagen-binding integrins and showed that the recombinant Scl protein p176 could promote cell adhesion and migration through α₂β₁ integrin. Using the I domain of α₂, we found that there are two binding site on p176 collagenous region. We further investigated the possible binding sequences using molecular modeling. Based on the modeling result, synthetic collagen-like peptides were created and compared in respect to their ability to bind to α₁I and α₂I. As result, I have identified several novel integrin-binding motifs and determined the specificity of each I domain toward these motifs.
"Submitted to the Graduate School of Biomedical Sciences of The Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy May 2006."
Approved as to style and content by: Magnus Höök, Benoit de Crombrugghe, Richard Mayne, Brad A. Amendt.
Ph. D. Texas A&M University System Health Science Center 2006.
Includes bibliographical references (leaves 97-110).