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Structural basis for the regulatory interactions of proapoptotic Par-4.

ABSTRACT: Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is masked upon dimerization indicating a potential mechanism for nuclear localization. The heteromeric-interaction models specifically showed that charge interaction is an important factor in the stability of heteromers of the C-terminal leucine zipper subdomain of Par-4 (Par-4LZ). These heteromer models also displayed NES masking capacity and therefore the ability to influence intracellular localization.

SUBMITTER: Tiruttani Subhramanyam UK

PROVIDER: S-EPMC5563986 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Structural basis for the regulatory interactions of proapoptotic Par-4.

Tiruttani Subhramanyam Udaya K UK Kubicek Jan J Eidhoff Ulf B UB Labahn Joerg J

Cell death and differentiation 20170616 9

Par-4 is a unique proapoptotic protein with the ability to induce apoptosis selectively in cancer cells. The X-ray crystal structure of the C-terminal domain of Par-4 (Par-4CC), which regulates its apoptotic function, was obtained by MAD phasing. Par-4 homodimerizes by forming a parallel coiled-coil structure. The N-terminal half of Par-4CC contains the homodimerization subdomain. This structure includes a nuclear export signal (Par-4NES) sequence, which is maske ...[more]

PMID: 28622290

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