MOESM1 of Identification of a tripartite interaction between the N-terminus of HIV-1 Vif and CBFβ that is critical for Vif function

Additional file 1: Supplementary Fig. S1. W38 and I57 are involved in maintaining the structural organization of the α-domain of Vif. A ribbon diagram of HIV-1 Vif highlighting residues W38, I57, I107, Y111, and F112 in blue. Vif is shown in red and CBFβ is shown in cyan (PDB: 4N9F). W38, I57, and I107 are not surface exposed (SASA 0.0 Å2); Y111 and F112 are only partially surface exposed (SASAs of 19.77 and 6.05 Å2, respectively)

Structural Analysis of the Active Site and DNA Binding of Human Cytidine Deaminase APOBEC3B

APOBEC3 (A3) proteins, a family of human cytidine deaminases, protect the host from endogenous retro-elements and exogenous viral infections by introducing hypermutations. However, overexpressed A3s can modify genomic DNA to promote tumorigenesis, especially A3B. Despite their overall similarity, A3 proteins have distinct deamination activity. Recently determined A3 structures have revealed the molecular determinants of nucleotide specificity and DNA binding. However, for A3B, the structural basis for regulation of deamination activity and the role of active site loops in coordinating DNA had remained unknown. Using advanced molecular modeling followed by experimental mutational analysis and dynamics simulations, we investigated the molecular mechanism of DNA binding by A3B-CTD. We modeled fully native A3B-DNA structure, and we identified Arg211 in loop 1 as the gatekeeper coordinating DNA and critical residue for nucleotide specificity. We also identified a unique autoinhibited conformation in A3B-CTD that restricts access and binding of DNA to the active site. Our results reveal the structural basis for DNA binding and relatively lower catalytic activity of A3B and provide opportunities for rational design of specific inhibitors to benefit cancer therapeutics

Nanoscale Characterization of Interaction of APOBEC3G with RNA

The human cytidine deaminase APOBEC3G (A3G) is a potent inhibitor of the HIV-1 virus in the absence of viral infectivity factor (Vif). The molecular mechanism of A3G antiviral activity is primarily attributed to deamination of single-stranded DNA (ssDNA); however, the nondeamination mechanism also contributes to HIV-1 restriction. The interaction of A3G with ssDNA and RNA is required for its antiviral activity. Here we used atomic force microscopy to directly visualize A3G–RNA and A3G–ssDNA complexes and compare them to each other. Our results showed that A3G in A3G–RNA complexes exists primarily in monomeric–dimeric states, similar to its stoichiometry in complexes with ssDNA. New A3G–RNA complexes in which A3G binds to two RNA molecules were identified. These data suggest the existence of two separate RNA binding sites on A3G. Such complexes were not observed with ssDNA substrates. Time-lapse high-speed atomic force microscopy was applied to characterize the dynamics of the complexes. The data revealed that the two RNA binding sites have different affinities for A3G. On the basis of the obtained results, a model for the interaction of A3G with RNA is proposed

Participant flow.

ObjectivesOne primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments.MethodWe compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay.ResultsA total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days [95% CI 8.1–11.8] vs. 9 days [95% CI 8.3–10.4], p = 0.157), the Weeks prognosis (32 days [95% CI 28.9–35.4] vs. 22 days [95% CI 20.3–22.9], p ConclusionIn this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.</div

Patient characteristics at enrollment.

ObjectivesOne primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments.MethodWe compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay.ResultsA total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days [95% CI 8.1–11.8] vs. 9 days [95% CI 8.3–10.4], p = 0.157), the Weeks prognosis (32 days [95% CI 28.9–35.4] vs. 22 days [95% CI 20.3–22.9], p ConclusionIn this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.</div

Symptoms and treatments until death.

ObjectivesOne primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments.MethodWe compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay.ResultsA total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days [95% CI 8.1–11.8] vs. 9 days [95% CI 8.3–10.4], p = 0.157), the Weeks prognosis (32 days [95% CI 28.9–35.4] vs. 22 days [95% CI 20.3–22.9], p ConclusionIn this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.</div

Kaplan-Meier survival curves stratified by the place of care for 3 groups defined according to Prognosis in Palliative Care Study predictor model A (PiPs-A): Days’ group (0–13 days), weeks’ group (14–55 days), and months’ group (≧56 days).

Kaplan-Meier survival curves stratified by the place of care for 3 groups defined according to Prognosis in Palliative Care Study predictor model A (PiPs-A): Days’ group (0–13 days), weeks’ group (14–55 days), and months’ group (≧56 days).</p

Cox proportional hazards analysis of survival time.

Cox proportional hazards analysis of survival time.</p