5LI1

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

Summary for 5LI1

• Entry DOI: 10.2210/pdb5li1/pdb
• Descriptor: Protein kinase C iota type, Par-3 partitioning defective 3 homolog (C. elegans), PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (7 entities in total)
• Functional Keywords: apkc, polarity, complex, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P41743
• Total number of polymer chains: 2
• Total formula weight: 43990.64

Authors

Soriano, E.V.,Purkiss, A.G.,McDonald, N.Q. (deposition date: 2016-07-13, release date: 2016-09-14, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2 Å)