InterPro domain: IPR038305

This N-terminal domain, HeLo, has a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation [ 1 ]. The domain is found exclusively in the fungal kingdom. Its structure, as it occurs in the heterokaryon incompatibility proteins HET-s and HET-S proteins, consists of two bundles of alpha-helices that pack into a single globular domain [ 2 ]. The domain boundary determined from its structure and from protease-resistance experiments overlaps with the C-terminal prion-forming domain of HET-s [ 2 ]. The HeLo domains of HET-s and HET-S are very similar and their few differences (and not the prion-forming domains) determine the compatibility-phenotype of the fungi in which the proteins are expressed.

The mechanism of the HeLo domain-function in heterokaryon-incompatibility is still under investigation, however the HeLo domain is found in similar protein architectures as other cell death and apoptosis-inducing domains. The only other HeLo protein to which a function has been associated is LopB from Leptosphaeria maculans [ 3 ]. Although its specific role in L. maculans is unknown, LopB- mutants have impaired ability to form lesions on oilseed rape. The HeLo domain is not related to the HET domain ( PF06985 ) which is another domain involved in heterokaryon incompatibility.

1. The mechanism of prion inhibition by HET-S. Mol. Cell 38, 889-99
2. Domain organization and structure-function relationship of the HET-s prion protein of Podospora anserina. EMBO J. 22, 2071-81
3. Comparative analysis of programmed cell death pathways in filamentous fungi. BMC Genomics 6, 177