BYU

Abstract by Austin Ellis

Personal Infomation


Presenter's Name

Austin Ellis

Degree Level

Undergraduate

Co-Authors

Kenneth Christensen
Eddie Lee

Abstract Infomation


Department

Chemistry and Biochemistry

Faculty Advisor

Kenneth Christensen

Title

The role of hyaline fibromatosis mutations in Capillary Morphogenesis Gene 2 loss of function.

Abstract

Hyaline Fibromatosis Syndromes (HFS) are caused by point mutations in capillary morphogenesis gene protein 2 (CMG2). Buildup of extracellular matrix/hyaline materials is associated with the symptoms observed in HFS and maintenance of extracellular matrix homeostasis is therefore a suggested role of CMG2. We have expressed the wildtype (WT) CMG2 and known HFS mutants and measured binding affinities to a CMG2 interactor, anthrax protective antigen (PA) by biolayer interferometry. We observe that certain mutations substantially reduce CMG2 binding to PA. These mutations potentially destabilize either the binding site to PA or overall CMG2 protein such that it doesn’t correctly localize to the plasma membrane. To elucidate a mechanism of change in function, we express HFS mutants as fluorescent protein fusions to see cellular localization. We observe that destabilization due to possible misfolding of CMG2 occurs in these mutants; hence, this is a plausible mechanism whereby normal recycling and clearance of extracellular matrix is reduced.