Evidence map›Paper›PMID 41380682›Full record

ArticleMolecular cell2025

HYPK promotes N-terminal protein acetylation through rapid ribosome exchange of NatA.

Alfred M Lentzsch, Ziyi Fan, Inayat U Irshad, Edward P O'Brien, Ajeet K Sharma, Rachel Green, Shu-Ou Shan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Alfred M LentzschDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Ziyi FanDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Inayat U IrshadDepartment of Physics, Indian Institute of Technology, Jammu 181221, India.
Edward P O'BrienDepartment of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
Ajeet K SharmaDepartment of Physics, Indian Institute of Technology, Jammu 181221, India; Department of Biosciences and Bioengineering, Indian Institute of Technology, Jammu 181221, India.
Rachel GreenDepartment of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Shu-Ou ShanDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: sshan@caltech.edu.

Funding

Supplement: Accurate Molecular Decision Making during Protein BiogenesisR35GM136321 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI Shu-ou Shan · 2020 to 2026
$6.7M
Translation Kinetics and their Effects on Protein Structure and Function, mRNA half-lives, and Cellular PhenotypeR35GM124818 · NIGMS · PENNSYLVANIA STATE UNIVERSITY, THE · PI Edward Patrick O'Brien · 2017 to 2026
$4.0M
NIGMS NIH HHS R35 GM124818NIGMS NIH HHS R35 GM136321
6 · The paper itself

Abstract

Numerous protein biogenesis factors cotranslationally facilitate the maturation of nascent proteins. Among them, N-terminal acetyltransferase A (NatA) acetylates the N terminus of ∼40% of the eukaryotic proteome. NatA is bound to Huntingtin-interacting protein K (HYPK), which inhibits NatA activity in vitro but enhances function in vivo. Here, kinetic and in-cell measurements resolve this paradox, showing that HYPK acts as a ribosome exchange factor for NatA. Without HYPK, hyper-tight ribosome binding prevents NatA from accessing additional ribosomes following each round of acetylation. HYPK accelerates NatA dissociation from the ribosome to license multiple turnovers, allowing a sub-stoichiometric level of this enzyme to globally acetylate the nascent proteome. Our results uncover a previously unidentified function of HYPK and demonstrate that a "Goldilocks" zone of ribosome interaction kinetics is required for cotranslational protein biogenesis machineries to act on all translating ribosomes in the cell.

Indexed as

N-Terminal Acetyltransferase ARibosomesAcetylationHEK293 CellsHumansKineticsProtein BindingProtein BiosynthesisProtein Processing, Post-TranslationalN-Terminal Acetyltransferase Acotranslational protein modificationexchange factorHYPKN-acetyltransferaseribosome

Identifiers

PMID41380682
PMCPMC12699156

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.