DNA/structural protein

PDB id

2gzk

Contents

			Protein chain

					159 a.a. *

			DNA/RNA

* Residue conservation analysis

PDB id:

2gzk

Links

Name:

DNA/structural protein

Title:

Structure of a complex of tandem hmg boxes and DNA

Structure:

Sex-determining region on y / hmgb1. Chain: a. Engineered: yes. 5'- d( Gp Gp Gp Ap Tp Cp Tp Ap Ap Ap Cp Ap Ap Tp Gp C)-3'. Chain: b. Engineered: yes. 5'- d( Gp Cp Ap Tp Tp Gp Tp Tp Tp Ap Gp Ap Tp Cp Cp C)-3'.

Source:

Homo sapiens, rattus rattus. Human, black rat. Organism_taxid: 9606,10117. Strain: ,. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic: yes

NMR struc:

1 models

Authors:

K.Stott,G.S.Tang,K.B.Lee,J.O.Thomas

Key ref:

K.Stott et al. (2006). Structure of a complex of tandem HMG boxes and DNA. J Mol Biol, 360, 90-104. PubMed id: 16813837 DOI: 10.1016/j.jmb.2006.04.059

Date:

11-May-06

Release date:

25-Jul-06

PROCHECK

	Headers

	References

Protein chain

P63159 (HMGB1_RAT) - High mobility group protein B1

Seq: Struc:					215 a.a. 159 a.a.*

Protein chain

Q6J4I5 (Q6J4I5_HUMAN) - Sex-determining region Y protein (Fragment)

Seq: Struc:					198 a.a. 159 a.a.*

Key:

PfamA domain

Secondary structure

* PDB and UniProt seqs differ at 119 residue positions (black crosses)



		Gene Ontology (GO) functional annotation

Cellular component	nucleus	1 term
Biological process	male sex determination	1 term
Biochemical function	protein binding	3 terms

DOI no: 10.1016/j.jmb.2006.04.059	J Mol Biol 360:90-104 (2006)
PubMed id: 16813837

Structure of a complex of tandem HMG boxes and DNA.
K.Stott, G.S.Tang, K.B.Lee, J.O.Thomas.

ABSTRACT

The high-mobility group protein HMGB1 contains two tandem DNA-binding HMG box domains, A and B, linked by a short flexible linker that allows the two domains to behave independently in the free protein. There is no structural information on how the linked domains and linker behave when bound to DNA, mainly due to the lack of any DNA-sequence preference of HMGB1. We report the structure determination, by NMR spectroscopy, of a well-defined complex of two tandem HMG boxes bound to a 16 bp oligonucleotide. The protein is an engineered version of the AB di-domain of HMGB1, in which the A box has been replaced by the HMG box of the sequence-specific transcription factor SRY, to give SRY.B. In the SRY.B/DNA complex, both HMG boxes bind in the minor groove and contribute to the overall DNA bending by intercalation of bulky hydrophobic residues between base-pairs; the bends reinforce each other, and the basic linker lies partly in the minor groove. As well as being the first structure of an HMG-box di-domain bound to DNA, this provides the first structure of the B domain of HMGB1 bound to DNA.

Selected figure(s)



	Figure 5. Figure 5. Structure of the SRY.B/DNA complex. (a) The lowest-energy structures (two views at 90°). Protein is shown in ribbon form (SRY box in red, linker in green and B box in blue) and bonds between DNA heavy-atoms are shown as continuous grey lines; the side-chains of the three intercalating residues are shown in stick form. The diagram was generated using MOLSCRIPT v.2.1.2.^64 (b)–(d) Ensembles of backbone structures for 20 energy-minimized conformations of the SRY.B/DNA complex, generated using MOLMOL:^65 (b) the whole complex; (c) residues 7–68 of SRY.B with nucleotides 9–25 of the DNA; (d) residues 89–157 of SRY.B with nucleotides 1–9 and 27–32 of the DNA. (e) Ensemble of DNA structures showing all heavy atoms.		Figure 6. Figure 6. Protein–DNA contacts in the SRY.B/DNA complex. (a) A representation of contacts (continuous lines) and key intermolecular NOEs (dotted lines). All contacts are in the DNA minor groove. The sites of intercalation of Ile13, Phe97 and Ile116 are indicated by grey boxes. Sugars labeled in red have a C3′-endo sugar pucker; the remainder are in the C2′-endo/C1′-exo conformation. (b) and (c) Views of the two ‘halves’ of the SRY.B/DNA complex generated using MOLSCRIPT v.2.1.2,^64 the B box in blue and the SRY box in red. Protein side-chains interacting with the DNA are shown as sticks; the intercalating residues (Ile13, Phe97 and Ile116) are rendered in CPK space-fill.

Figures were selected by the author.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20564205

J.S.Han, H.A.Kim, S.Lee, and M.Lee (2010).
VEGF receptor binding peptide-linked high mobility box group-1 box A as a targeting gene carrier for hypoxic endothelial cells.

J Cell Biochem, 110, 1094-1100.

19288517

J.S.Han, K.Kim, and M.Lee (2009).
A high mobility group B-1 box A peptide combined with an artery wall binding peptide targets delivery of nucleic acids to smooth muscle cells.

J Cell Biochem, 107, 163-170.

19129233

J.Zhang, M.J.McCauley, L.J.Maher, M.C.Williams, and N.E.Israeloff (2009).
Mechanism of DNA flexibility enhancement by HMGB proteins.

Nucleic Acids Res, 37, 1107-1114.

19173290

M.J.McCauley, and M.C.Williams (2009).
Optical tweezers experiments resolve distinct modes of DNA-protein binding.

Biopolymers, 91, 265-282.

19726587

S.Ray, and A.Grove (2009).
The yeast high mobility group protein HMO2, a subunit of the chromatin-remodeling complex INO80, binds DNA ends.

Nucleic Acids Res, 37, 6389-6399.

19120473

S.Saitoh, and K.Miyake (2009).
Regulatory molecules required for nucleotide-sensing Toll-like receptors.

Immunol Rev, 227, 32-43.

19755502

T.S.Wong, S.Rajagopalan, S.M.Freund, T.J.Rutherford, A.Andreeva, F.M.Townsley, M.Petrovich, and A.R.Fersht (2009).
Biophysical characterizations of human mitochondrial transcription factor A and its binding to tumor suppressor p53.

Nucleic Acids Res, 37, 6765-6783.

18380906

A.N.Kriatchko, S.Bergeron, and P.C.Swanson (2008).
HMG-box domain stimulation of RAG1/2 cleavage activity is metal ion dependent.

BMC Mol Biol, 9, 32.

18347754

K.Kim, J.S.Han, H.A.Kim, and M.Lee (2008).
Expression, purification and characterization of TAT-high mobility group box-1A peptide as a carrier of nucleic acids.

Biotechnol Lett, 30, 1331-1337.

18515834

N.A.Becker, J.D.Kahn, and L.J.Maher (2008).
Eukaryotic HMGB proteins as replacements for HU in E. coli repression loop formation.

Nucleic Acids Res, 36, 4009-4021.

18976912

S.C.Lee, N.Corradi, E.J.Byrnes, S.Torres-Martinez, F.S.Dietrich, P.J.Keeling, and J.Heitman (2008).
Microsporidia evolved from ancestral sexual fungi.

Curr Biol, 18, 1675-1679.

18838393

Y.Jiang, and M.M.Howe (2008).
Regional mutagenesis of the gene encoding the phage Mu late gene activator C identifies two separate regions important for DNA binding.

Nucleic Acids Res, 36, 6396-6405.

17417641

J.Tian, A.M.Avalos, S.Y.Mao, B.Chen, K.Senthil, H.Wu, P.Parroche, S.Drabic, D.Golenbock, C.Sirois, J.Hua, L.L.An, L.Audoly, G.La Rosa, A.Bierhaus, P.Naworth, A.Marshak-Rothstein, M.K.Crow, K.A.Fitzgerald, E.Latz, P.A.Kiener, and A.J.Coyle (2007).
Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE.

Nat Immunol, 8, 487-496.

17964600

M.J.McCauley, J.Zimmerman, L.J.Maher, and M.C.Williams (2007).
HMGB binding to DNA: single and double box motifs.

J Mol Biol, 374, 993.

17397256

S.Mahony, P.E.Auron, and P.V.Benos (2007).
DNA familial binding profiles made easy: comparison of various motif alignment and clustering strategies.

PLoS Comput Biol, 3, e61.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.