PDBsum entry 5d68

Signaling protein

PDB id: 5d68

Contents

Protein chains

433 a.a.

Waters ×66

PDB id:

5d68

Name:

Signaling protein

Title:

Crystal structure of krit1 ard-ferm

Structure:

Krev interaction trapped protein 1. Chain: a, b, c. Fragment: ard-ferm domain (unp residues 52-529). Synonym: krev interaction trapped 1, cerebral cavernous malformations 1 protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: krit1, ccm1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.91Å R-factor: 0.209 R-free: 0.246

Authors:

R.Zhang,X.Li,T.J.Boggon

Key ref:

R.Zhang et al. (2015). Structural analysis of the KRIT1 ankyrin repeat and FERM domains reveals a conformationally stable ARD-FERM interface. J Struct Biol, 192, 449-456. PubMed id: 26458359 DOI: 10.1016/j.jsb.2015.10.006

Date:

11-Aug-15 Release date: 21-Oct-15

Protein chains

O00522  (KRIT1_HUMAN) -  Krev interaction trapped protein 1 from Homo sapiens

Seq: 736 a.a.

Struc: 433 a.a.

DOI no: 10.1016/j.jsb.2015.10.006

J Struct Biol 192:449-456 (2015)

PubMed id: 26458359

Structural analysis of the KRIT1 ankyrin repeat and FERM domains reveals a conformationally stable ARD-FERM interface.

R.Zhang, X.Li, T.J.Boggon.

ABSTRACT

Cerebral cavernous malformations (CCM) are vascular dysplasias that usually occur in the brain and are associated with mutations in the KRIT1/CCM1, CCM2/MGC4607/OSM/Malcavernin, and PDCD10/CCM3/TFAR15 genes. Here we report the 2.9Å crystal structure of the ankyrin repeat domain (ARD) and FERM domain of the protein product of KRIT1 (KRIT1; Krev interaction trapped 1). The crystal structure reveals that the KRIT1 ARD contains 4 ankyrin repeats. There is an unusual conformation in the ANK4 repeat that is stabilized by Trp-404, and the structure reveals a solvent exposed ankyrin groove. Domain orientations of the three copies within the asymmetric unit suggest a stable interaction between KRIT1 ARD and FERM domains, indicating a globular ARD-FERM module. This resembles the additional F0 domain found N-terminal to the FERM domain of talin. Structural analysis of KRIT1 ARD-FERM highlights surface regions of high evolutionary conservation, and suggests potential sites that could mediate interaction with binding partners. The structure therefore provides a better understanding of KRIT1 at the molecular level.