PDBsum entry: 1p7h

Transcription/DNA

PDB id: 1p7h

Contents

Protein chains

286 a.a. *

DNA/RNA

Waters ×189

* Residue conservation analysis

PDB id:

1p7h

Name:

Transcription/DNA

Title:

Structure of nfat1 bound as a dimer to the HIV-1 ltr kb element

Structure:

5'- d( Ap Ap Tp Gp Gp Gp Gp Ap Cp Tp Tp Tp Cp Cp A)-3'. Chain: a, c. Engineered: yes. 5'- d( Tp Tp Tp Gp Gp Ap Ap Ap Gp Tp Cp Cp Cp Cp A)-3'. Chain: b, d. Engineered: yes. Nuclear factor of activated t-cells, cytoplasmic

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Gene: nfatc2 or nfat1 or nfatp

Biol. unit:

Octamer (from PQS)

Resolution:

2.60Å R-factor: 0.231 R-free: 0.265

Authors:

M.J.Giffin,J.C.Stroud,D.L.Bates,K.D.Von Koenig,J.Hardin, L.Chen

Key ref:

M.J.Giffin et al. (2003). Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element. Nat Struct Biol, 10, 800-806. PubMed id: 12949493 DOI: 10.1038/nsb981

Date:

01-May-03 Release date: 23-Sep-03

Protein chains

Q13469  (NFAC2_HUMAN) -  Nuclear factor of activated T-cells, cytoplasmic 2

Seq: 925 a.a.

Struc: 286 a.a.*

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

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: regulation of transcription (2 terms)
• Biochemical function: transcription factor activity (1 term)

DOI no: 10.1038/nsb981

Nat Struct Biol 10:800-806 (2003)

PubMed id: 12949493

Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element.

M.J.Giffin, J.C.Stroud, D.L.Bates, K.D.von Koenig, J.Hardin, L.Chen.

ABSTRACT

DNA binding by NFAT1 as a dimer has been implicated in the activation of host and viral genes. Here we report a crystal structure of NFAT1 bound cooperatively as a dimer to the highly conserved kappa B site from the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR). This structure reveals a new mode of dimerization and protein-DNA recognition by the Rel homology region (RHR) of NFAT1. The two NFAT1 monomers form a complete circle around the kappa B DNA through protein-protein interactions mediated by both their N- and C-terminal subdomains. The major dimer interface, formed by the C-terminal domain, is asymmetric and substantially different from the symmetric dimer interface seen in other Rel family proteins. Comparison to other NFAT structures, including NFAT5 and the NFAT1-Fos-Jun-ARRE2 complex, reveals that NFAT1 adopts different conformations and its protein surfaces mediate distinct protein-protein interactions in the context of different DNA sites.

Selected figure(s)

Figure 4.
Figure 4. E'F loop interactions. (a) Detailed interactions between the E'F loops of the two NFAT1 monomers bound to the HIV-1 LTR B site viewed from underneath the DNA with respect to Figure 1a. Residues from the E'F loop that bind DNA in the minor groove and phosphate backbone are also shown together with the narrowed DNA minor groove. (b) Differential DNA binding by the NFAT1 dimer on 10-bp (HIV-1 LTR) and 9-bp (human IL-8 promoter) B sites lead to different E'F loop orientation and therefore different protein-protein interactions between the RHR-N of the NFAT1 dimer. For clarity, only the AB loop and the E'F loop helix (E'F H) of each monomer are shown. One monomer (green) is anchored at one half site indicated by the green base pair at position 1. The AB loop of the gray monomer (AB loop, 9 bp) recognizes a 9-bp B site indicated by the gray base pair at position 9, its E'F loop helix (E'F H, 9 bp) swings away from the E'F H of the green monomer. The AB loop of the magenta monomer (AB loop, 10 bp) recognizes a 10-bp B site indicated by the magenta base pair at position 10; its E'F loop helix (E'F H, 10 bp) moves close to the E'F H of the green monomer.

Figure 5.
Figure 5. Context-specific functions of the NFAT1 protein surface. Left, a surface model of NFAT1 (monomer B of Fig. 1a) showing specific protein surface areas of the RHR involved in different protein-protein interactions on different promoter elements. The contacting surface of Fos (red), Jun (blue), RHR-C dimerization (light blue) and E'F loop dimerization (yellow) are colored differently. The orange area (the cc' loop of the RHR-C) indicates protein surface with overlapping functions (contacting Fos and RHR-C dimerization). Right, the same surface model viewed 90° away from the left panel.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 800-806) copyright 2003.

Figures were selected by the author.