Structure of puromycin-sensitive aminopeptidase and polyglutamine binding

Sowmya Madabushi, K. Martin Chow, Eun Suk Song, Anwesha Goswami, Louis B. Hersh, David W. Rodgers

Research output: Contribution to journalArticlepeer-review


Puromycin-sensitive aminopeptidase (E.C., UniProt P55786), a zinc metallopeptidase belonging to the M1 family, degrades a number of bioactive peptides as well as peptides released from the proteasome, including polyglutamine. We report the crystal structure of PSA at 2.3 Å´ . Overall, the enzyme adopts a V-shaped architecture with four domains characteristic of the M1 family aminopeptidases, but it is in a less compact conformation compared to most M1 enzymes of known structure. A microtubule binding sequence is present in a C-terminal HEAT repeat domain of the enzyme in a position where it might serve to mediate interaction with tubulin. In the catalytic metallopeptidase domain, an elongated active site groove lined with aromatic and hydrophobic residues and a large S1 subsite may play a role in broad substrate recognition. The structure with bound polyglutamine shows a possible interacting mode of this peptide, which is supported by mutation.

Original languageEnglish
Article numbere0287086
JournalPLoS ONE
Issue number7 July
StatePublished - Jul 2023

Bibliographical note

Publisher Copyright:
Copyright: © 2023 Madabushi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ASJC Scopus subject areas

  • General


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