Research Article: Structural analysis of a replication protein encoded by a plasmid isolated from a multiple sclerosis patient

Date Published: May 01, 2019

Publisher: International Union of Crystallography

Author(s): Turgay Kilic, Alexander N. Popov, Amelie Burk-Körner, Anna Koromyslova, Harald zur Hausen, Timo Bund, Grant S. Hansman.


The crystal structure of the WH1 domain of the eukaryotic replication initiator protein (Rep) MSBI1.176 in the dimeric form has been determined to 1.53 Å resolution and shows a number of structural similarities to and differences from other known prokaryotic Reps.

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The consumption of bovine meat and milk is considered to be a risk factor for the development of colon and breast cancers (Chan et al., 2011 ▸; Corpet, 2011 ▸; Huxley et al., 2009 ▸). Indeed, epidemiologic data suggest that there is a correlation of these cancers with the consumption of bovine products from cattle derived from Eurasian aurochs (zur Hausen & de Villiers, 2015 ▸; zur Hausen et al., 2017 ▸; zur Hausen, 2012 ▸). Recently, it was suggested that bovine meat and milk factors (BMMFs), which are circular, single-stranded episomal DNAs (<3 kb) that are found in bovine meat and milk products, might represent a possible etiological agent of such diseases (Funk et al., 2014 ▸; Falida et al., 2017 ▸; zur Hausen et al., 2019 ▸). More recently, BMMFs were isolated from patients with multiple sclerosis and studies suggested these to be a possible infectious agent of this disease (Whitley et al., 2014 ▸; Lamberto et al., 2014 ▸; Gunst et al., 2014 ▸; zur Hausen et al., 2019 ▸). Reps are important for the replication of plasmids or autarkic episomal nucleic acids in different hosts. It is speculated that such proteins and Rep-encoding DNAs might be linked to disease. Thus, careful structural and functional characterization of Reps is needed. The Rep described in this study is encoded by the human bioactive bovine meat and milk factor MSBI1.176, which was isolated from a patient with multiple sclerosis (Whitley et al., 2014 ▸). Rep-specific serum antibodies have been found in a set of healthy human blood-bank donors, indicating general human exposure to such agents (Eile­brecht et al., 2018 ▸). The discovery that this MSBI1.176-encoded Rep WH1 protein was closely similar to a prokaryote Rep structure might have important consequences and point towards a possible disease-correlated adaptation of these agents towards humans. This new structural information might aid in the development and design of therapeutic/preventive drugs that can inhibit these Reps of diverse origin.   Source:


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