6ppl | pdb_00006ppl

Cryo-EM structure of human NatE complex (NatA/Naa50)

Loading... Status: waiting for Mol* initialization Structural highlights 6ppl is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACO, IHP NonStd Res: ACE Gene: NAA50, MAK3, NAT13, NAT5 (HUMAN), NAA15, GA19, NARG1, NATH, TBDN100 (HUMAN), NAA10, ARD1, ARD1A, TE2 (HUMAN) Activity: N-terminal amino-acid N(alpha)-acetyltransferase NatA, with EC number 2.3.1.255 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NAA10_HUMAN] Premature aging appearance-developmental delay-cardiac arrhythmia syndrome;Microphthalmia, Lenz type. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function [NAA50_HUMAN] Probable catalytic component of the NAA11-NAA15 complex which displays alpha (N-terminal) acetyltransferase activity. [NAA10_HUMAN] Catalytic subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity (PubMed:15496142, PubMed:19826488, PubMed:19420222, PubMed:20145209, PubMed:27708256, PubMed:25489052). Acetylates amino termini that are devoid of initiator methionine (PubMed:19420222). The alpha (N-terminal) acetyltransferase activity may be important for vascular, hematopoietic and neuronal growth and development. Without NAA15, displays epsilon (internal) acetyltransferase activity towards HIF1A, thereby promoting its degradation (PubMed:12464182). Represses MYLK kinase activity by acetylation, and thus represses tumor cell migration (PubMed:19826488). Acetylates, and stabilizes TSC2, thereby repressing mTOR activity and suppressing cancer development (PubMed:20145209). Acetylates HSPA1A and HSPA1B at 'Lys-77' which enhances its chaperone activity and leads to preferential binding to co-chaperone HOPX (PubMed:27708256). Acts as a negative regulator of sister chromatid cohesion during mitosis (PubMed:27422821). [NAA15_HUMAN] Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity. The NAT activity may be important for vascular, hematopoietic and neuronal growth and development. Required to control retinal neovascularization in adult ocular endothelial cells. In complex with XRCC6 and XRCC5 (Ku80), up-regulates transcription from the osteocalcin promoter. Publication Abstract from PubMed The human N-terminal acetyltransferase E (NatE) contains NAA10 and NAA50 catalytic, and NAA15 auxiliary subunits and associates with HYPK, a protein with intrinsic NAA10 inhibitory activity. NatE co-translationally acetylates the N-terminus of half the proteome to mediate diverse biological processes, including protein half-life, localization, and interaction. The molecular basis for how NatE and HYPK cooperate is unknown. Here, we report the cryo-EM structures of human NatE and NatE/HYPK complexes and associated biochemistry. We reveal that NAA50 and HYPK exhibit negative cooperative binding to NAA15 in vitro and in human cells by inducing NAA15 shifts in opposing directions. NAA50 and HYPK each contribute to NAA10 activity inhibition through structural alteration of the NAA10 substrate-binding site. NAA50 activity is increased through NAA15 tethering, but is inhibited by HYPK through structural alteration of the NatE substrate-binding site. These studies reveal the molecular basis for coordinated N-terminal acetylation by NatE and HYPK. Molecular basis for N-terminal acetylation by human NatE and its modulation by HYPK.,Deng S, McTiernan N, Wei X, Arnesen T, Marmorstein R Nat Commun. 2020 Feb 10;11(1):818. doi: 10.1038/s41467-020-14584-7. PMID:32042062 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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