Figure S1 Specificity controls for binding by Spo0A-DBD-his6. Arrows indicate the position of shifted species (DNA:protein complexes). Titrations with PCR fragments of PabrB (containing a high affinity binding site) and PtcdA (lacking such a site) correspond to approximately 0.1 nM/mL -0.03 nM/ mL. A. Comparison of binding of Spo0A-DBD-his6, Spo0A-his6 and CD2195-his6 binding to the upstream region of spoIIAA. B. Binding of Spo0A-DBD-his6 to the upstream region of spoIIAA is reversed by the addition of PabrB, but not by the addition of PtcdA). C. Binding of Spo0A-DBD-his6 to the upstream region of spoIIE is reversed by the addition of PabrB, but not by the addition of PtcdA. D. Binding of Spo0A-DBD-his6 to the upstream region of spoIIGA is reversed by the addition of PabrB, but not by the addition of PtcdA. E. Binding of Spo0A-DBD-his6 to the upstream region of tcdB is reversed by the addition of PabrB, but not by the addition of PtcdA. F. Binding of Spo0A-DBD-his6 to the upstream region of tcdC is not or moderately affected by the addition of PabrB and/or PtcdA. (TIF) Text S1 Oligonucleotides used in this study and PCR cycling conditions for the EMSA probes. (PDF) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001 Approximately 2 billion people have been infected with human hepatitis B virus (HBV) worldwide. Over 350 million people currently are chronically infected and are at high risk for progression to cirrhosis, liver failure, or cancer. More than 50% of liver cancers worldwide are attributed to HBV infection. HBV-related liver diseases remain a major public health problem, causing approximately 1 million deaths per year. Individuals coinfected with HBV and HDV are at greater risk for rapid progression and severe disease (Lavanchy, 2004; Hughes et al., 2011) . Despite its enormous medical and social relevance, progress in HBV research has been impeded by the lack of understanding of HBV entry by which the virus specifically infects human liver cells. HBV is an enveloped virus containing a small genome of 3.2 kb of partially double-stranded DNA encoding four overlapping reading frames. The HBV envelope consists of the small (S), middle (M), and large (L) envelope proteins, which are multiple transmembrane spanners sharing the same C-terminal domain corresponding to the S protein but differing at their N-terminal domains ( Figure 1A ) (Heermann et al., 1984; Seeger et al., 2007) . HDV is a small satellite RNA virus of HBV carrying all three HBV envelope proteins and can only propagate when coexisting with HBV. The mechanism of viral entry of HDV is believed to be similar to that of HBV, and HDV has been used as a surrogate for studying HBV infection at the entry level (Barrera et al., 2004; Sureau, 2006; Hughes et al., 2011) . The L protein and integrity of S protein are critical for HBV