Dynamic conformations of nucleophosmin (NPM1) at a key monomer-monomer interface affect oligomer stability and interactions with granzyme B.

ABSTRACT: Nucleophosmin (NPM1) is an abundant, nucleolar tumor antigen with important roles in cell proliferation and putative contributions to oncogenesis. Wild-type NPM1 forms pentameric oligomers through interactions at the amino-terminal core domain. A truncated form of NPM1 found in some hepatocellular carcinoma tissue formed an unusually stable oligomer and showed increased susceptibility to cleavage by granzyme B. Initiation of translation at the seventh methionine generated a protein (M7-NPM) that shared all these properties. We used deuterium exchange mass spectrometry (DXMS) to perform a detailed structural analysis of wild-type NPM1 and M7-NPM, and found dynamic conformational shifts or local "unfolding" at a specific monomer-monomer interface which included the β-hairpin "latch." We test

SUBMITTER: Duan-Porter WD 

PROVIDER: S-EPMC4260957 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature