PDBsum entry 2lg1

Metal binding protein

PDB id: 2lg1

Contents

Protein chain

185 a.a.

PDB id:

2lg1

Name:

Metal binding protein

Title:

Solution structure of the human akap13 ph domain and stabilizing dh helix

Structure:

A-kinase anchor protein 13. Chain: a. Fragment: ph domain residues 2164-2346. Synonym: akap-13, akap-lbc, breast cancer nuclear receptor-binding auxiliary protein, guanine nucleotide exchange factor lbc, human thyroid-anchoring protein 31, lymphoid blast crisis oncogene, lbc oncogene, non-oncogenic rho gtpase-specific gtp exchange factor, protein kinase a-anchoring protein 13, p47. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: akap13, brx, ht31, lbc. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

M.Lenoir,M.Sugawara,L.Ball,M.Overduin

Key ref:

M.Lenoir et al. (2014). Structural insights into the activation of the RhoA GTPase by the lymphoid blast crisis (Lbc) oncoprotein. J Biol Chem, 289, 23992-24004. PubMed id: 24993829

Date:

19-Jul-11 Release date: 03-Aug-11

Protein chain

Q12802  (AKP13_HUMAN) -  A-kinase anchor protein 13 from Homo sapiens

Seq: 2813 a.a.

Struc: 185 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

J Biol Chem 289:23992-24004 (2014)

PubMed id: 24993829

Structural insights into the activation of the RhoA GTPase by the lymphoid blast crisis (Lbc) oncoprotein.

M.Lenoir, M.Sugawara, J.Kaur, L.J.Ball, M.Overduin.

ABSTRACT

The small GTPase RhoA promotes deregulated signaling upon interaction with lymphoid blast crisis (Lbc), the oncogenic form of A-kinase anchoring protein 13 (AKAP13). The onco-Lbc protein is a hyperactive Rho-specific guanine nucleotide exchange factor (GEF), but its structural mechanism has not been reported despite its involvement in cardiac hypertrophy and cancer causation. The pleckstrin homology (PH) domain of Lbc is located at the C-terminal end of the protein and is shown here to specifically recognize activated RhoA rather than lipids. The isolated dbl homology (DH) domain can function as an independent activator with an enhanced activity. However, the DH domain normally does not act as a solitary Lbc interface with RhoA-GDP. Instead it is negatively controlled by the PH domain. In particular, the DH helical bundle is coupled to the structurally dependent PH domain through a helical linker, which reduces its activity. Together the two domains form a rigid scaffold in solution as evidenced by small angle x-ray scattering and (1)H,(13)C,(15)N-based NMR spectroscopy. The two domains assume a "chair" shape with its back possessing independent GEF activity and the PH domain providing a broad seat for RhoA-GTP docking rather than membrane recognition. This provides structural and dynamical insights into how DH and PH domains work together in solution to support regulated RhoA activity. Mutational analysis supports the bifunctional PH domain mediation of DH-RhoA interactions and explains why the tandem domain is required for controlled GEF signaling.