PDBsum entry 3w8h

Protein binding/transferase

PDB id: 3w8h

Contents

Protein chains

190 a.a.

66 a.a.

Ligands

SO4 ×7

Waters ×116

PDB id:

3w8h

Name:

Protein binding/transferase

Title:

Crystal structure of ccm3 in complex with thE C-terminal regulatory domain of stk25

Structure:

Programmed cell death protein 10. Chain: a. Fragment: unp residues 8-212. Synonym: cerebral cavernous malformations 3 protein, tf-1 cell apoptosis-related protein 15. Engineered: yes. Serine/threonine-protein kinase 25. Chain: b. Fragment: unp residues 355-426.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ccm3, pdcd10, tfar15. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: sok1, stk25, ysk1.

Resolution:

2.43Å R-factor: 0.212 R-free: 0.264

Authors:

X.Xu,D.C.Wang,J.Ding

Key ref:

X.Xu et al. (2013). Structural basis for the unique heterodimeric assembly between cerebral cavernous malformation 3 and germinal center kinase III. Structure, 21, 1059-1066. PubMed id: 23665169 DOI: 10.1016/j.str.2013.04.007

Date:

13-Mar-13 Release date: 03-Jul-13

Protein chain

Q9BUL8  (PDC10_HUMAN) -  Programmed cell death protein 10 from Homo sapiens

Seq: 212 a.a.

Struc: 190 a.a.

Protein chain

O00506  (STK25_HUMAN) -  Serine/threonine-protein kinase 25 from Homo sapiens

Seq: 426 a.a.

Struc: 66 a.a.*

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

Enzyme reactions

• Enzyme class: Chain B: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.str.2013.04.007

Structure 21:1059-1066 (2013)

PubMed id: 23665169

Structural basis for the unique heterodimeric assembly between cerebral cavernous malformation 3 and germinal center kinase III.

X.Xu, X.Wang, Y.Zhang, D.C.Wang, J.Ding.

ABSTRACT

Defects in cerebral cavernous malformation protein CCM3 result in cerebral cavernous malformation (CCM), a common vascular lesion of the human CNS. CCM3 functions as an adaptor protein that interacts with various signal proteins. Among these partner proteins, germinal center kinase III (GCKIII) proteins have attracted significant interest because GCKIII-CCM3 interactions play essential roles in vascular physiology. Here, we report the crystal structures of CCM3 in complex with the C-terminal regulatory domains of GCKIII (GCKIIIct) at 2.4 Å resolution. Our results reveal that GCKIIIct adopts a fold closely resembling that of the CCM3 N-terminal dimeric domain. GCKIIIct heterodimerizes with CCM3 in a manner analogous to CCM3 homodimerization. The remarkable structural rearrangement of CCM3 induced by GCKIIIct binding and the ensuing interactions within CCM3 are characterized as the structural determinants for GCKIIIct-CCM3 heterodimerization. Taken together, these findings provide a precise structural basis for GCKIIIct-CCM3 heterodimerization and the functional performance of GCKIII mediated by CCM3.