N-degron pathways

A Varshavsky - Proceedings of the National Academy of Sciences, 2024 - pnas.org
An N-degron is a degradation signal whose main determinant is a “destabilizing” N-terminal
residue of a protein. Specific N-degrons, discovered in 1986, were the first identified …

The social and structural architecture of the yeast protein interactome

AC Michaelis, AD Brunner, M Zwiebel, F Meier… - Nature, 2023 - nature.com
Cellular functions are mediated by protein–protein interactions, and mapping the
interactome provides fundamental insights into biological systems. Affinity purification …

FAM72A degrades UNG2 through the GID/CTLH complex to promote mutagenic repair during antibody maturation

P Barbulescu, CK Chana, MK Wong… - Nature …, 2024 - nature.com
A diverse antibody repertoire is essential for humoral immunity. Antibody diversification
requires the introduction of deoxyuridine (dU) mutations within immunoglobulin genes to …

Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases

DC Scott, S Chittori, N Purser, MT King… - Nature …, 2024 - nature.com
Specificity of the ubiquitin-proteasome system depends on E3 ligase-substrate interactions.
Many such pairings depend on E3 ligases binding to peptide-like sequences-termed N-or C …

mTORC1-CTLH E3 ligase regulates the degradation of HMG-CoA synthase 1 through the Pro/N-degron pathway

SA Yi, S Sepic, BA Schulman, A Ordureau, H An - Molecular Cell, 2024 - cell.com
Mammalian target of rapamycin (mTOR) senses changes in nutrient status and stimulates
the autophagic process to recycle amino acids. However, the impact of nutrient stress on …

Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1

J Düring, M Wolter, JJ Toplak, C Torres… - Nature Structural & …, 2024 - nature.com
Ubiquitin ligases (E3s) are pivotal specificity determinants in the ubiquitin system by
selecting substrates and decorating them with distinct ubiquitin signals. However, structure …

Identification and classification of papain-like cysteine proteinases

F Ozhelvaci, K Steczkiewicz - Journal of Biological Chemistry, 2023 - ASBMB
Papain-like cysteine peptidases form a big and highly diverse superfamily of proteins
involved in many important biological functions, such as protein turnover, deubiquitination …

Privileged proteins with a second residence: dual targeting and conditional re‐routing of mitochondrial proteins

O Pines, M Horwitz, JM Herrmann - The FEBS Journal, 2024 - Wiley Online Library
Almost all mitochondrial proteins are encoded by nuclear genes and synthesized in the
cytosol as precursor proteins. Signals in the amino acid sequence of these precursors …

Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism

KV Gottemukkala, J Chrustowicz, D Sherpa, S Sepic… - Molecular Cell, 2024 - cell.com
The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of
complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of …

The hGIDGID4 E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration

H Bagci, M Winkler, B Grädel, F Uliana… - Life Science …, 2024 - life-science-alliance.org
The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating
multiple cellular processes, including cell cycle progression and metabolism. However, the …