The Angiomotin (Amot) family of adaptor proteins directly integrates the signaling that controls cellular differentiation and cell growth. Amot family members bind core polarity proteins that control the organization of the apical domain of epithelial cells as well as Yap, a transcriptional co-activator that appears to be the key regulator of cell growth. A critical feature of all Amot proteins is a novel lipid binding domain, the Amot coiled-coil homology (ACCH) domain, which confers its association with membranes and affects membrane curvature. This domain, while sharing some features of BAR domains, i.e. a predicted coiled coil fold of approximately 240 residues, also has unique properties including the ability to selectively bind monophosphorylated phosphatidylinositols (PI).Amot ACCH domain shares 56% sequence identity with that of AmotL2, and 68% with that of AmotL1; however it has been documented that these proteins modulate different cellular actions in cellular migration, proliferation and differentiation. The goal of this project is to delineate the structure of the various ACCH domains, thereby suggesting possible routes to modulate their activity associated with ductal hyperplasia, and later breast cancer. Preliminary structures of the Amot80 and AmotL2 ACCH domains presented in this work were determined from SAXS data.This work was supported by NIH R01-AA18123S1, NIH K01CA169078-01, and NSF LSAMP-IUPUI.

Towards determining the structures of Angiomotin coiled-coil homology domains

246th National Meeting (2013)

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