7MHZ

Human Hedgehog acyltransferase (HHAT) in complex with a palmitoylated Hedgehog peptide product and a Fab antibody fragment

Summary for 7MHZ

• Entry DOI: 10.2210/pdb7mhz/pdb
• EMDB information: 23837
• Descriptor: Sonic hedgehog protein N-product peptide, Protein-cysteine N-palmitoyltransferase HHAT, 3H02 Fab heavy chain, ... (8 entities in total)
• Functional Keywords: mboat, goat, porcupine, acyl transferase, membrane protein, membrane enzyme, er, palmitoyl-coa, transferase-immune system complex, transferase/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 148470.20

Authors

Long, S.B.,Jiang, Y. (deposition date: 2021-04-16, release date: 2021-06-16, Last modification date: 2024-10-09)

Primary citation

Jiang, Y.,Benz, T.L.,Long, S.B.
Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.
Science, 372:1215-1219, 2021

PubMed Abstract: Hedgehog proteins govern crucial developmental steps in animals and drive certain human cancers. Before they can function as signaling molecules, Hedgehog precursor proteins must undergo amino-terminal palmitoylation by Hedgehog acyltransferase (HHAT). We present cryo-electron microscopy structures of human HHAT in complex with its palmitoyl-coenzyme A substrate and of a product complex with a palmitoylated Hedgehog peptide at resolutions of 2.7 and 3.2 angstroms, respectively. The structures reveal how HHAT overcomes the challenges of bringing together substrates that have different physiochemical properties from opposite sides of the endoplasmic reticulum membrane within a membrane-embedded active site for catalysis. These principles are relevant to related enzymes that catalyze the acylation of Wnt and of the appetite-stimulating hormone ghrelin. The structural and mechanistic insights may advance the development of inhibitors for cancer.

PubMed: 34112694
DOI: 10.1126/science.abg4998

Experimental method

ELECTRON MICROSCOPY (3.2 Å)