PDBsum entry 4zp3

Signaling protein

PDB id: 4zp3

Contents

Protein chains

(+ 1 more) 43 a.a.

39 a.a.

38 a.a.

28 a.a.

28 a.a.

27 a.a.

30 a.a.

Metals

_CD ×4

Waters ×63

PDB id:

4zp3

Name:

Signaling protein

Title:

Akap18:pka-riialpha structure reveals crucial anchor points for recognition of regulatory subunits of pka

Structure:

Camp-dependent protein kinase type ii-alpha regulatory subunit. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Engineered: yes. A-kinase anchor protein 7 isoforms alpha and beta. Chain: m, n, o, p, q, r. Fragment: unp residues 43-82. Synonym: akap-7 isoforms alpha and beta,a-kinase anchor protein 18 kda,akap 18,protein kinase a-anchoring protein 7 isoforms alpha/beta,

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prkar2a, pkr2, prkar2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: akap7, akap15, akap18. Expression_system_taxid: 562

Resolution:

2.63Å R-factor: 0.225 R-free: 0.268

Authors:

F.Goetz,Y.Roske,K.Faelber,K.Zuehlke,K.Autenrieth,A.Kreuchwig, G.Krause,F.W.Herberg,O.Daumke,U.Heinemann,E.Klussmann

Key ref:

F.Götz et al. (2016). AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA. Biochem J, 473, 1881-1894. PubMed id: 27102985 DOI: 10.1042/BCJ20160242

Date:

07-May-15 Release date: 04-May-16

Protein chains

P13861  (KAP2_HUMAN) -  cAMP-dependent protein kinase type II-alpha regulatory subunit from Homo sapiens

Seq: 404 a.a.

Struc: 43 a.a.

Protein chains

P13861  (KAP2_HUMAN) -  cAMP-dependent protein kinase type II-alpha regulatory subunit from Homo sapiens

Seq: 404 a.a.

Struc: 39 a.a.

Protein chains

P13861  (KAP2_HUMAN) -  cAMP-dependent protein kinase type II-alpha regulatory subunit from Homo sapiens

Seq: 404 a.a.

Struc: 38 a.a.

Protein chain

Q9P0M2  (AKA7G_HUMAN) -  A-kinase anchor protein 7 isoform gamma from Homo sapiens

Seq: 348 a.a.

Struc: 28 a.a.

Protein chain

Q9P0M2  (AKA7G_HUMAN) -  A-kinase anchor protein 7 isoform gamma from Homo sapiens

Seq: 348 a.a.

Struc: 28 a.a.

Protein chains

Q9P0M2  (AKA7G_HUMAN) -  A-kinase anchor protein 7 isoform gamma from Homo sapiens

Seq: 348 a.a.

Struc: 27 a.a.

Protein chain

Q9P0M2  (AKA7G_HUMAN) -  A-kinase anchor protein 7 isoform gamma from Homo sapiens

Seq: 348 a.a.

Struc: 30 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R: E.C.?

DOI no: 10.1042/BCJ20160242

Biochem J 473:1881-1894 (2016)

PubMed id: 27102985

AKAP18:PKA-RIIα structure reveals crucial anchor points for recognition of regulatory subunits of PKA.

F.Götz, Y.Roske, M.S.Schulz, K.Autenrieth, D.Bertinetti, K.Faelber, K.Zühlke, A.Kreuchwig, E.J.Kennedy, G.Krause, O.Daumke, F.W.Herberg, U.Heinemann, E.Klussmann.

ABSTRACT

A-kinase anchoring proteins (AKAPs) interact with the dimerization/docking (D/D) domains of regulatory subunits of the ubiquitous protein kinase A (PKA). AKAPs tether PKA to defined cellular compartments establishing distinct pools to increase the specificity of PKA signalling. Here, we elucidated the structure of an extended PKA-binding domain of AKAP18β bound to the D/D domain of the regulatory RIIα subunits of PKA. We identified three hydrophilic anchor points in AKAP18β outside the core PKA-binding domain, which mediate contacts with the D/D domain. Such anchor points are conserved within AKAPs that bind regulatory RII subunits of PKA. We derived a different set of anchor points in AKAPs binding regulatory RI subunits of PKA. In vitro and cell-based experiments confirm the relevance of these sites for the interaction of RII subunits with AKAP18 and of RI subunits with the RI-specific smAKAP. Thus we report a novel mechanism governing interactions of AKAPs with PKA. The sequence specificity of each AKAP around the anchor points and the requirement of these points for the tight binding of PKA allow the development of selective inhibitors to unequivocally ascribe cellular functions to the AKAP18-PKA and other AKAP-PKA interactions.