ABSTRACT
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In 1963 I joined the laboratory of Karl Piez at the National Institute for Dental Research. This assignment satisfied my national service obligation as a physician during the Vietnam War. Karl was interested in the structure of the triple helical protein, type I collagen, the only collagen type known at the time (there are now at least 28 genetically distinct collagen types known in mammals). Karl had previously shown that soluble collagen, i.e., collagen that could be extracted from animal and human skin, or from some other tissues by non-denaturing solvents such as cold acetic acid, consisted of two identical chains termed α1, and a third homologous chain, α2. These chains were identified by their characteristic positions of elution during carboxy methyl (CM) cellulose chromatography, and by their amino acid compositions. However, α1/α1 and α1/α2 dimers, termed β11 and β12, respectively, could also be identified, based on their sedimentation equilibrium patterns during ultracentrifugation and by their amino acid compositions. These dimers were linked by covalent bonds, since they could not be dissociated by heat or by denaturing agents such as urea or guanidine. Furthermore, the majority of the collagen in skin, and to even a greater extent in tissues such as tendon or ligament, could not be solubilized, even with denaturing agents. The collagen in these tissues was clearly stabilized by covalent bonds, but what was the chemical nature of these bonds, and was there a relation between the inter-chain bonds in soluble β components and those in insoluble collagen?
