A structural census links penultimate-residue class to N-terminal burial in human protein assemblies
- 1Saint Louis University Medical School
Abstract
Initiator methionine excision is an early step in protein maturation, but where it might influence protein complex assembly remains poorly understood. This study asked which human protein N-terminal positions engage assembly partners and whether their interface environments point to specific roles for methionine removal. A survey of 7,246 deposited human biological assemblies compared 1,123 eligible proteins. N-terminal positions in MetAP-permissive residue-2 classes were less often interface-engaged than those in nonpermissive classes (37.5% versus 47.5%; adjusted odds ratio 0.65). Nevertheless, 261 permissive-class proteins showed substantial engagement in at least one modeled assembly, including 175 candidates retained after filtering for observed terminal boundaries. Partner-resolved comparisons of proteasome subunits PSMA7, PSMA6 and PSMA4 revealed distinct neighboring-subunit, assembly-chaperone and multi-partner environments. Thus, the possible importance of methionine removal depends not only on sequence, but also on which partner an N-terminal position encounters in a particular assembly context. This structural atlas identifies candidates for direct tests of how verified terminal processing affects partner engagement, complex assembly and function.
Related
- Discovering and designing multistate protein assemblies
- Structural control of Fe(II)-based multivalent glycan assemblies enables intramolecular avidity and ultra-high-affinity binding
- Thermodynamic and Structural Evidence for Higher-Order Selegiline with Carboxymethyl-β-Cyclodextrin Supramolecular Assemblies in Aqueous Solution.
- Chemical and Structural Characterization of Eucalyptus sp. Wood Residue–Poly(vinyl acetate) Composites
- AMIA: an automated workflow for analysing the structural and dynamic effects of protein variants
BibTeX
@misc{chang2026structural,
title = {{A structural census links penultimate-residue class to N-terminal burial in human protein assemblies}},
author = {Y.-H. Chang},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748389},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748389v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A structural census links penultimate-residue class to N-terminal burial in human protein assemblies
AU - Y.-H. Chang
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748389
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748389v1
AB - Initiator methionine excision is an early step in protein maturation, but where it might influence protein complex assembly remains poorly understood. This study asked which human protein N-terminal positions engage assembly partners and whether their interface environments point to specific roles for methionine removal. A survey of 7,246 deposited human biological assemblies compared 1,123 eligible proteins. N-terminal positions in MetAP-permissive residue-2 classes were less often interface-engaged than those in nonpermissive classes (37.5% versus 47.5%; adjusted odds ratio 0.65). Nevertheless, 261 permissive-class proteins showed substantial engagement in at least one modeled assembly, including 175 candidates retained after filtering for observed terminal boundaries. Partner-resolved comparisons of proteasome subunits PSMA7, PSMA6 and PSMA4 revealed distinct neighboring-subunit, assembly-chaperone and multi-partner environments. Thus, the possible importance of methionine removal depends not only on sequence, but also on which partner an N-terminal position encounters in a particular assembly context. This structural atlas identifies candidates for direct tests of how verified terminal processing affects partner engagement, complex assembly and function.
ER -