Supplementary Materials

Supplementary Material for:

A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent

Noemi Gioelli, Federica Maione, Chiara Camillo, Michela Ghitti, Donatella Valdembri, Noemi Morello, Marie Darche, Lorena Zentilin, Gabriella Cagnoni, Yaqi Qiu, Mauro Giacca, Maurizio Giustetto, Michel Paques, Ilaria Cascone, Giovanna Musco, Luca Tamagnone, Enrico Giraudo,* Guido Serini*

*Corresponding author. Email: guido.serini{at}ircc.it (G.S.); enrico.giraudo{at}ircc.it (E.G.)

Published 23 May 2018, Sci. Transl. Med. 10, eaah4807 (2018)
DOI: 10.1126/scitranslmed.aah4807

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Purification of Fc-tagged SEMA3A_ΔIg-b and SEMA3A_A106K_ΔIg-b recombinant proteins.
  • Fig. S2. SEMA3A_ΔIg-b protein effect on tumor growth in RIP-Tag2 mice.
  • Fig. S3. SEMA6A-PLXNA2 and SEMA3AA106K-PLXNA4 interaction details.
  • Fig. S4. Structural comparison of key residues involved in the charge complementarity of the extrusion region.
  • Fig. S5. Root mean square deviation of the backbone atoms from the starting SEMA6A-PLXNA2 and SEMA3AA106K-PLXNA4 structures as a function of time.
  • Fig. S6. Root mean square fluctuation of α-carbon atoms of SEMA6A-PLXNA2 and SEMA3AA106K-PLXNA4 structures.
  • Fig. S7. B-factor analysis.
  • Fig. S8. SEMA3A_A106K_ΔIg-b mutant protein isoform binding to PLXNA4 in the presence or the absence of NRP1.
  • Fig S9. SEMA3B_A105K_ΔIg-b mutant protein isoform binding to PLXNA2.
  • Fig. S10. Testing SEMA3A_A106K_ΔIg-b mutant isoform in EC collapse assays.
  • Fig. S11. NRP1-independent SEMA3A_A106K_ΔIg-b biochemical signaling in ECs.
  • Fig. S12. Comparing SEMA3A_ΔIg-b and SEMA3A_A106K_ΔIg-b effects on tumor growth in RIP-Tag2 and mPDAC.
  • Fig. S13. Monitoring the effect of SEMA3A_A106K_ΔIg-b protein on mPDAC tumor growth over time.
  • Fig. S14. Toxicology analysis of SEMA3A_A106K_ΔIg-b protein–treated mice.
  • Fig. S15. Rotarod motor performance analysis of SEMA3A_A106K_ΔIg-b protein–treated mice.
  • Fig. S16. Effect of SEMA3A_A106K_ΔIg-b protein on laser-induced CNV of the mouse retina.
  • Table S1. Analysis of the electrostatic heterodimer interfaces.
  • Table S2. Biochemical analysis of renal and hepatic function parameters.
  • Table S3. Hematological profiling of all the treatment groups compared with the controls.
  • References (7289)

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Other Supplementary Material for this manuscript includes the following:

  • Table S4. Raw data (provided as an Excel file).