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Dual roles of the Sterol Recognition Region in Hedgehog protein modification

biorxiv. 2020; 
Rahul Purohit,  Daniel S. Peng,  Erika Vielmas,  Alison E. Ondrus
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Peptide Synthesis Peptides for residues encompassing the 1st helix (368-391) and 2nd helix (431-449) of the hSHH SRR were obtained from Genscript Inc. at ≥90% purity. Crude soybean phospholipids containing L-α-phosphatidylcholine (PC, Sigma-Aldrich, P5638) were used to prepare liposomes for CD analysis. Briefly, phospholipids in the presence or absence of cholesterol were dissolved in chloroform and dried to a thin layer on the sides of a glass vial using a rotary evaporator. Get A Quote

摘要

Nature provides a number of mechanisms to encode dynamic information in biomolecules. In metazoans, there exist rare chemical modifications that occur through entirely unique mechanistic regimes. One such example occurs in the Hedgehog (Hh) morphogens, proteins singular across all domains of life for the nature of their covalent ligation to cholesterol. The isoform- and context-specific efficiency of the ligation reaction has profound impact on the activity of Hh morphogens and represents an unexplored aspect of Hh ligand-dependent cancers. To elucidate the chemical mechanism of this modification, we have defined roles of the uncharacterized sterol recognition region (SRR) in Hh proteins. We use a combination o... More

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