This project will use high-resolution solid-state nuclear magnetic resonance (NMR) to characterize the conformational changes which accompany the mineralization of elastin in the heritable vascular and dermal disorder called pseudoxanthoma elasticum (PXE). The normal elastic fiber lends resiliency to vertebrate tissues, such as the skin and blood vessels. Its major protein component is elastin, which imparts elasticity to these tissues. Elastin is an insoluble, amorphous, and extensively crosslinked biopolymer, and there are no high-resolution crystallographic or solution NMR structures for this protein. Changes in elastic fiber morphology have been associated with the loss of elasticity in heritable and acquired disorders such as Marfan syndrome, supravalvular aortic stenosis, and aortic aneurysms. And, recent work by other laboratories strongly suggests that the calcification of the elastic fibers in PXE patients is a secondary consequence of a primary alteration in the structure and/or assembly of elastin. Therefore, we propose that PXE effects the introduction of new components or abnormal concentrations of typical components in elastic tissue. The abnormal chemical conditions induce conformational changes of elastin, and it is this abnormal state which undergoes mineralization. To obtain the most definitive descriptions of structural changes to elastin on the molecular level, high-resolution solid-state NMR spectroscopy will be utilized. These studies will identify the structural differences between normal elastin and several calcified states, as produced in well-defined chemical conditions. And, the characterization of the abnormal elastin, as found in the tissue of a PXE patient, will be indicative of the conditions which accompany, or even induce, mineralization.