2KDT

PC1/3 DCSG sorting domain structure in DPC

2KDT の概要

• エントリーDOI: 10.2210/pdb2kdt/pdb
• 分子名称: Neuroendocrine convertase 1 (1 entity in total)
• 機能のキーワード: secretory granules, prohorme convertase, calcium, cleavage on pair of basic residues, cytoplasmic vesicle, glycoprotein, hydrolase, protease, serine protease, zymogen, protein transport
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasmic vesicle, secretory vesicle: P63239
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5275.73

構造登録者

Dikeakos, J.D.,Di Lello, P.,Lacombe, M.J.,Ghirlando, R.,Legault, P.,Reudelhuber, T.L.,Omichinski, J.G. (登録日: 2009-01-19, 公開日: 2009-04-07, 最終更新日: 2024-05-22)

主引用文献

Dikeakos, J.D.,Di Lello, P.,Lacombe, M.J.,Ghirlando, R.,Legault, P.,Reudelhuber, T.L.,Omichinski, J.G.
Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease.
Proc.Natl.Acad.Sci.USA, 106:7408-7413, 2009

PubMed Abstract: Several peptide hormones are initially synthesized as inactive precursors. It is only on entry of these prohormones and their processing proteases into dense core secretory granules (DCSGs) that the precursors are cleaved to generate their active forms. Prohormone convertase (PC)1/3 is a processing protease that is targeted to DCSGs. The signal for targeting PC1/3 to DCSGs resides in its carboxy-terminal tail (PC1/3(617-753)), where 3 regions (PC1/3(617-625), PC1/3(665-682), and PC1/3(711-753)) are known to aid in sorting and membrane association. In this article, we have determined a high-resolution structure of the extreme carboxy-terminal sorting domain, PC1/3(711-753) in micelles by NMR spectroscopy. PC1/3(711-753) contains 2 alpha helices located between residues 722-728 and 738-750. Functional assays demonstrate that the second helix (PC1/3(738-750)) is necessary and sufficient to target a constitutively secreted protein to granules, and that L(745) anchors a hydrophobic patch that is critical for sorting. Also, we demonstrate that calcium binding by the second helix of PC1/3(711-753) promotes aggregation of the domain via the hydrophobic patch centered on L(745). These results provide a structure-function analysis of a DCSG-sorting domain, and reveal the importance of a hydrophobic patch and calcium binding in controlling the sorting of proteins containing alpha helices to DCSGs.

PubMed: 19376969
DOI: 10.1073/pnas.0809576106

実験手法

SOLUTION NMR