6C95

The Human NatA (Naa10/Naa15) amino-terminal acetyltransferase complex bound to HYPK

Summary for 6C95

• Entry DOI: 10.2210/pdb6c95/pdb
• Related: 6C9M
• Descriptor: N-alpha-acetyltransferase 15, NatA auxiliary subunit, N-alpha-acetyltransferase 10, Huntingtin-interacting protein K, ... (5 entities in total)
• Functional Keywords: nata, hypk, n-terminal acetylation, huntingtin interacting protein, protein complex, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 143299.66

Authors

Gottlieb, L.,Marmorstein, R. (deposition date: 2018-01-25, release date: 2018-06-06, Last modification date: 2024-10-23)

Primary citation

Gottlieb, L.,Marmorstein, R.
Structure of Human NatA and Its Regulation by the Huntingtin Interacting Protein HYPK.
Structure, 26:925-, 2018

PubMed Abstract: Co-translational N-terminal protein acetylation regulates many protein functions including degradation, folding, interprotein interactions, and targeting. Human NatA (hNatA), one of six conserved metazoan N-terminal acetyltransferases, contains Naa10 catalytic and Naa15 auxiliary subunits, and associates with the intrinsically disordered Huntingtin yeast two-hybrid protein K (HYPK). We report on the crystal structures of hNatA and hNatA/HYPK, and associated biochemical and enzymatic analyses. We demonstrate that hNatA contains unique features: a stabilizing inositol hexaphosphate (IP) molecule and a metazoan-specific Naa15 domain that mediates high-affinity HYPK binding. We find that HYPK harbors intrinsic hNatA-specific inhibitory activity through a bipartite structure: a ubiquitin-associated domain that binds a hNaa15 metazoan-specific region and an N-terminal loop-helix region that distorts the hNaa10 active site. We show that HYPK binding blocks hNaa50 targeting to hNatA, likely limiting Naa50 ribosome localization in vivo. These studies provide a model for metazoan NAT activity and HYPK regulation of N-terminal acetylation.

PubMed: 29754825
DOI: 10.1016/j.str.2018.04.003

Experimental method

X-RAY DIFFRACTION (3.15 Å)