Additional information for poster “Distinct structural features of the iRhom homology domain (IRHD) regulate ADAM17 interaction and forward trafficking.”
3rd International Symposium
Protease World in Health and Disease
Supplementary material
Figure S1
(A) Structural model of the IRHD and the rhomboid core of iRhom2 created with AlphaFold 2.
(B) Multiple sequence alignment of iRhoms reveal a highly conserved motif (iCERES) in a region without secondary structures as well as a hypervariable loop.
Figure S2
Comparison of experimentally derived substructures with AlphaFold 2 and AlphaFold Multimer The low root-mean-square deviation (RMSD) from the correct atomic positions demonstrates high accuracy of prediction.
Figure S3
(A) To avoid disturbing the folding of the rhomboid core, we bridged the gap between TMH1 and TMH2 with a long linker.
(B) Local structure of iCERES. W538, W545 and I542 form a hydrophobic core.
(C) Other mutations in iCERES show that disruption of the hydrophobic core has the most drastic effects. Mutation of other positions in iCERES also reduces the efficiency of iCERES function (forward traffic), but not as drastically as mutation of the hydrophobic core.
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Cooperations
Dr. Nicole Schwarz - MOCA, RWTH UK Aachen
Dr. Christian Preisinger - IZKF Aachen
Dr. Petr Kasparek and Dr. Radislav Sedlacek - ASCR Prague