期刊名称：The Indiana University Journal of Undergraduate Research
印刷版ISSN：2379-5611
出版年度：2018
卷号：4
期号：1
页码：1-20
出版社：Indiana University Bloomington
摘要：Angiomotins (Amots) are a family of adapter proteins that modulate cellular polarity, differentiation, proliferation, and migration.
Amot family members have a characteristic lipid-binding domain, the coiled coil homology (ACCH) domain that selectively targets the
protein to membranes, which has been directly linked to its regulatory role in the cell. Several spot blot assays were used to validate the
regions of the domain that participate in its membrane association, deformation, and vesicle fusion activity, which indicated the need
for a structure to define the mechanism. Therefore, we sought to understand the structure-function relationship of this domain in order
to find ways to modulate these signaling pathways. After many failed attempts to crystallize the ACCH domain of each Amot family
member for structural analysis, we decided to pursue homologous models that could be refined using small angle x-ray scattering data.
Theoretical models were produced using the homology software SWISS-MODEL and threading software I-TASSER and LOMETS,
followed by comparison to SAXS data for model selection and refinement. We present a theoretical model of the domain that is driven
by alpha helices and short random coil regions. These alpha helical regions form a classic dimer interface followed by two wide spread
legs that we predict to be the lipid binding interface.
