9E7A

Crystal structure of the MIR domain of the S. cerevisiae mannosyltransferase Pmt4 in Complex with Ccw5

これはPDB形式変換不可エントリーです。

9E7A の概要

• エントリーDOI: 10.2210/pdb9e7a/pdb
• 分子名称: Dolichyl-phosphate-mannose--protein mannosyltransferase 4, Cell wall mannoprotein CIS3, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• 機能のキーワード: pmt4, ccw5, o-mannosylation, membrane protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 78059.24

構造登録者

Du, M.,Yuan, Z.,Li, H. (登録日: 2024-11-01, 公開日: 2025-10-15, 最終更新日: 2025-11-19)

主引用文献

Du, M.,Yuan, Z.,Kovach, A.,Lyu, M.,Li, H.
Pmt4 recognizes two separate acceptor sites to O-mannosylate in the S/T-rich regions of substrate proteins.
Nat Commun, 16:9726-9726, 2025

PubMed Abstract: Protein O-mannosyltransferases (PMTs) add mannose to serine/threonine (S/T)-rich proteins in the endoplasmic reticulum, facilitating proper folding and trafficking through the secretory pathway. These enzymes share a conserved architecture that includes a large transmembrane domain housing the catalytic pocket and a lumenal β-trefoil-folded MIR domain. Although S/T-rich regions in acceptor proteins are generally disordered, it remains unclear how PMTs selectively target these regions over other intrinsically disordered sequences. Here, using cryo-EM and X-ray crystallography, we demonstrate that the Saccharomyces cerevisiae Pmt4 dimer recognizes an S/T-rich peptide at two distinct sites. A groove above the catalytic pocket in the transmembrane domain binds the mannose-accepting S/T site, while the lumenal MIR domain engages an S/T-X-S/T motif. Notably, the substrate peptide is simultaneously bound by the catalytic pocket of one Pmt4 protomer and the MIR domain of the other, revealing an unexpected cooperative dual substrate recognition mechanism. This mechanism likely underpins the invariant dimeric architecture observed in all PMT family members.

PubMed: 41188226
DOI: 10.1038/s41467-025-64729-9

実験手法

X-RAY DIFFRACTION (1.69 Å)