PDBsum entry 1v06

DNA binding protein

PDB id: 1v06

Contents

Protein chain

138 a.a. *

* Residue conservation analysis

PDB id:

1v06

Name:

DNA binding protein

Title:

Axh domain of the transcription factor hbp1 from m.Musculus

Structure:

Hmg box-containing protein 1. Chain: a. Fragment: axh domain, residues 208-345. Synonym: hbp1, hmg-box containing protein-1, hmg box transcription factor 1, high mobility group box transcription factor 1. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

C.De Chiara,G.Kelly,A.Pastore

Key ref:

C.de Chiara et al. (2005). The AXH domain adopts alternative folds the solution structure of HBP1 AXH. Structure, 13, 743-753. PubMed id: 15893665 DOI: 10.1016/j.str.2005.02.016

Date:

24-Mar-04 Release date: 21-Apr-05

Protein chain

Q8R316  (HBP1_MOUSE) -  HMG box-containing protein 1 from Mus musculus

Seq: 516 a.a.

Struc: 138 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.str.2005.02.016

Structure 13:743-753 (2005)

PubMed id: 15893665

The AXH domain adopts alternative folds the solution structure of HBP1 AXH.

C.de Chiara, R.P.Menon, S.Adinolfi, J.de Boer, E.Ktistaki, G.Kelly, L.Calder, D.Kioussis, A.Pastore.

ABSTRACT

AXH is a protein module identified in two unrelated families that comprise the transcriptional repressor HBP1 and ataxin-1 (ATX1), the protein responsible for spinocerebellar ataxia type-1 (SCA1). SCA1 is a neurodegenerative disorder associated with protein misfolding and formation of toxic intranuclear aggregates. We have solved the structure in solution of monomeric AXH from HBP1. The domain adopts a nonclassical permutation of an OB fold and binds nucleic acids, a function previously unidentified for this region of HBP1. Comparison of HBP1 AXH with the crystal structure of dimeric ATX1 AXH indicates that, despite the significant sequence homology, the two proteins have different topologies, suggesting that AXH has chameleon properties. We further demonstrate that HBP1 AXH remains monomeric, whereas the ATX1 dimer spontaneously aggregates and forms fibers. Our results describe an entirely novel, to our knowledge, example of a chameleon fold and suggest a link between these properties and the SCA1 pathogenesis.

Selected figure(s)

Figure 2.
Figure 2. Comparison between the AXH Domains of ATX1 and HBP1
(A) Structure of the dimer of dimers of ATX1 as observed in the crystal structure (PDB identifier 1oa8). The subunits (A–D from left to right) are alternatively indicated with dark and light tones of green. Red circles indicate the intermolecular interfaces between each monomer in the dimer and between the two asymmetric dimers. They include the N terminus and helix α[1], respectively.
(B) Structures of subunits A and B of the AXH from ATX1.
(C) Structure of HBP1_AXH (left) and superposition of the A subunit of ATX1 AXH and HBP1_AXH (right). Only the structurally similar regions are displayed. The positions of the N and C termini and of the secondary structure elements are indicated. Figure 2. Comparison between the AXH Domains of ATX1 and HBP1(A) Structure of the dimer of dimers of ATX1 as observed in the crystal structure (PDB identifier 1oa8). The subunits (A–D from left to right) are alternatively indicated with dark and light tones of green. Red circles indicate the intermolecular interfaces between each monomer in the dimer and between the two asymmetric dimers. They include the N terminus and helix α[1], respectively.(B) Structures of subunits A and B of the AXH from ATX1.(C) Structure of HBP1_AXH (left) and superposition of the A subunit of ATX1 AXH and HBP1_AXH (right). Only the structurally similar regions are displayed. The positions of the N and C termini and of the secondary structure elements are indicated.

Figure 6.
Figure 6. Tendency of ATX1_AXH to Aggregate
(A) Elution profiles of analytical gel filtration experiments performed on a freshly purified ATX1_AXH sample (100 μM protein concentration in 20 mM Tris-HCl (pH 8.0), 20 mM NaCl, 2 mM β-mercaptoethanol). The protein was incubated at 22°C and was injected in the column immediately after concentration (continuous line) after 24 hr (dashed line), 3 days (dotted line), and 4 days (dotted and dashed line).
(B) EM micrograph of a sample of ATX1_AXH treated as in (A) but incubated at 37°C for 24 hr.
(C) For comparison, EM micrograph of an HBP1_AXH treated as in (B). The bar corresponds to 50 nm. Figure 6. Tendency of ATX1_AXH to Aggregate(A) Elution profiles of analytical gel filtration experiments performed on a freshly purified ATX1_AXH sample (100 μM protein concentration in 20 mM Tris-HCl (pH 8.0), 20 mM NaCl, 2 mM β-mercaptoethanol). The protein was incubated at 22°C and was injected in the column immediately after concentration (continuous line) after 24 hr (dashed line), 3 days (dotted line), and 4 days (dotted and dashed line).(B) EM micrograph of a sample of ATX1_AXH treated as in (A) but incubated at 37°C for 24 hr.(C) For comparison, EM micrograph of an HBP1_AXH treated as in (B). The bar corresponds to 50 nm.

The above figures are reprinted by permission from Cell Press: Structure (2005, 13, 743-753) copyright 2005.

Figures were selected by an automated process.