5ICW

Crystal structure of human NatF (hNaa60) homodimer bound to Coenzyme A

Summary for 5ICW

• Entry DOI: 10.2210/pdb5icw/pdb
• Descriptor: N-alpha-acetyltransferase 60, COENZYME A, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: transferase, acetylation, gnat, nat
• Biological source: Homo sapiens (Human)
• Cellular location: Golgi apparatus membrane : Q9H7X0
• Total number of polymer chains: 4
• Total formula weight: 86282.31

Authors

Stove, S.I.,Magin, R.S.,Marmorstein, R.,Arnesen, T. (deposition date: 2016-02-23, release date: 2016-06-22, Last modification date: 2024-01-10)

Primary citation

Stve, S.I.,Magin, R.S.,Foyn, H.,Haug, B.E.,Marmorstein, R.,Arnesen, T.
Crystal Structure of the Golgi-Associated Human N alpha-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation.
Structure, 24:1044-1056, 2016

PubMed Abstract: N-Terminal acetylation is a common and important protein modification catalyzed by N-terminal acetyltransferases (NATs). Six human NATs (NatA-NatF) contain one catalytic subunit each, Naa10 to Naa60, respectively. In contrast to the ribosome-associated NatA to NatE, NatF/Naa60 specifically associates with Golgi membranes and acetylates transmembrane proteins. To gain insight into the molecular basis for the function of Naa60, we developed an Naa60 bisubstrate CoA-peptide conjugate inhibitor, determined its X-ray structure when bound to CoA and inhibitor, and carried out biochemical experiments. We show that Naa60 adapts an overall fold similar to that of the catalytic subunits of ribosome-associated NATs, but with the addition of two novel elongated loops that play important roles in substrate-specific binding. One of these loops mediates a dimer to monomer transition upon substrate-specific binding. Naa60 employs a catalytic mechanism most similar to Naa50. Collectively, these data reveal the molecular basis for Naa60-specific acetyltransferase activity with implications for its Golgi-specific functions.

PubMed: 27320834
DOI: 10.1016/j.str.2016.04.020

Experimental method

X-RAY DIFFRACTION (1.951 Å)