2WVO

Structure of the HET-S N-terminal domain

Summary for 2WVO

• Entry DOI: 10.2210/pdb2wvo/pdb
• Related: 2WVN 2WVQ
• Descriptor: SMALL S PROTEIN, CHLORIDE ION (3 entities in total)
• Functional Keywords: prion-binding protein, prion regulatory domain, heterokaryon incompatibility
• Biological source: PODOSPORA ANSERINA
• Total number of polymer chains: 2
• Total formula weight: 52455.31

Authors

Greenwald, J.,Buhtz, C.,Ritter, C.,Kwiatkowski, W.,Choe, S.,Saupe, S.J.,Riek, R. (deposition date: 2009-10-19, release date: 2010-07-28, Last modification date: 2023-12-20)

Primary citation

Greenwald, J.,Buhtz, C.,Ritter, C.,Kwiatkowski, W.,Choe, S.,Maddelein, M.L.,Ness, F.,Cescau, S.,Soragni, A.,Leitz, D.,Saupe, S.J.,Riek, R.
The Mechanism of Prion Inhibition by Het-S.
Mol.Cell, 38:889-, 2010

PubMed Abstract: HET-S (97% identical to HET-s) has an N-terminal globular domain that exerts a prion-inhibitory effect in cis on its own prion-forming domain (PFD) and in trans on HET-s prion propagation. We show that HET-S fails to form fibrils in vitro and that it inhibits HET-s PFD fibrillization in trans. In vivo analyses indicate that beta-structuring of the HET-S PFD is required for HET-S activity. The crystal structures of the globular domains of HET-s and HET-S are highly similar, comprising a helical fold, while NMR-based characterizations revealed no differences in the conformations of the PFDs. We conclude that prion inhibition is not encoded by structure but rather in stability and oligomerization properties: when HET-S forms a prion seed or is incorporated into a HET-s fibril via its PFD, the beta-structuring in this domain induces a change in its globular domain, generating a molecular species that is incompetent for fibril growth.

PubMed: 20620958
DOI: 10.1016/J.MOLCEL.2010.05.019

Experimental method

X-RAY DIFFRACTION (2.3 Å)