5LI1

Structure of a Par3-inhibitory peptide bound to PKCiota core kinase domain

5LI1 の概要

• エントリーDOI: 10.2210/pdb5li1/pdb
• 分子名称: Protein kinase C iota type, Par-3 partitioning defective 3 homolog (C. elegans), PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (7 entities in total)
• 機能のキーワード: apkc, polarity, complex, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cytoplasm : P41743
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43990.64

構造登録者

Soriano, E.V.,Purkiss, A.G.,McDonald, N.Q. (登録日: 2016-07-13, 公開日: 2016-09-14, 最終更新日: 2024-01-10)

主引用文献

Soriano, E.V.,Ivanova, M.E.,Fletcher, G.,Riou, P.,Knowles, P.P.,Barnouin, K.,Purkiss, A.,Kostelecky, B.,Saiu, P.,Linch, M.,Elbediwy, A.,Kjr, S.,O'Reilly, N.,Snijders, A.P.,Parker, P.J.,Thompson, B.J.,McDonald, N.Q.
aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization.
Dev.Cell, 38:384-398, 2016

PubMed Abstract: Atypical protein kinase C (aPKC) is a key apical-basal polarity determinant and Par complex component. It is recruited by Par3/Baz (Bazooka in Drosophila) into epithelial apical domains through high-affinity interaction. Paradoxically, aPKC also phosphorylates Par3/Baz, provoking its relocalization to adherens junctions (AJs). We show that Par3 conserved region 3 (CR3) forms a tight inhibitory complex with a primed aPKC kinase domain, blocking substrate access. A CR3 motif flanking its PKC consensus site disrupts the aPKC kinase N lobe, separating P-loop/αB/αC contacts. A second CR3 motif provides a high-affinity anchor. Mutation of either motif switches CR3 to an efficient in vitro substrate by exposing its phospho-acceptor site. In vivo, mutation of either CR3 motif alters Par3/Baz localization from apical to AJs. Our results reveal how Par3/Baz CR3 can antagonize aPKC in stable apical Par complexes and suggests that modulation of CR3 inhibitory arms or opposing aPKC pockets would perturb the interaction, promoting Par3/Baz phosphorylation.

PubMed: 27554858
DOI: 10.1016/j.devcel.2016.07.018

実験手法

X-RAY DIFFRACTION (2 Å)