PDBsum entry 4kfz

Transcription

PDB id: 4kfz

Contents

Protein chains

146 a.a.

127 a.a.

Metals

_ZN ×8

PDB id:

4kfz

Name:

Transcription

Title:

Crystal structure of lmo2 and anti-lmo2 vh complex

Structure:

Lmo-2. Chain: a, b. Fragment: unp residues 9-158. Synonym: rhombotin-2, cysteine-rich protein ttg-2, lim domain only protein 2, t-cell translocation protein 2. Engineered: yes. Anti-lmo2 vh. Chain: c, d. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: lmo2, rbtn2, rbtnl1, rhom2, ttg2. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: anti-lmo2 vh. Expression_system_taxid: 562

Resolution:

2.80Å R-factor: 0.240 R-free: 0.258

Authors:

H.Sewell,T.Tanaka,K.El Omari,A.Cruz-Migoni,E.J.Mancini,N.Fuentes- Fernandez,J.Chambers,T.H.Rabbitts

Key ref:

H.Sewell et al. (2014). Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex. Sci Rep, 4, 3643. PubMed id: 24407558 DOI: 10.1038/srep03643

Date:

28-Apr-13 Release date: 22-Jan-14

Protein chains

P25791  (RBTN2_HUMAN) -  Rhombotin-2 from Homo sapiens

Seq: 158 a.a.

Struc: 146 a.a.

Protein chains

P01764  (HV323_HUMAN) -  Immunoglobulin heavy variable 3-23 from Homo sapiens

Seq: 117 a.a.

Struc: 127 a.a.*

* PDB and UniProt seqs differ at 16 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

DOI no: 10.1038/srep03643

Sci Rep 4:3643 (2014)

PubMed id: 24407558

Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex.

H.Sewell, T.Tanaka, K.El Omari, E.J.Mancini, A.Cruz, N.Fernandez-Fuentes, J.Chambers, T.H.Rabbitts.

ABSTRACT

LMO2 was discovered via chromosomal translocations in T-cell leukaemia and shown normally to be essential for haematopoiesis. LMO2 is made up of two LIM only domains (thus it is a LIM-only protein) and forms a bridge in a multi-protein complex. We have studied the mechanism of formation of this complex using a single domain antibody fragment that inhibits LMO2 by sequestering it in a non-functional form. The crystal structure of LMO2 with this antibody fragment has been solved revealing a conformational difference in the positioning and angle between the two LIM domains compared with its normal binding. This contortion occurs by bending at a central helical region of LMO2. This is a unique mechanism for inhibiting an intracellular protein function and the structural contusion implies a model in which newly synthesized, intrinsically disordered LMO2 binds to a partner protein nucleating further interactions and suggests approaches for therapeutic targeting of LMO2.