PDBsum entry 1a02

Transcription/DNA

PDB id: 1a02

Contents

Protein chains

280 a.a. *

53 a.a. *

52 a.a. *

DNA/RNA

Waters ×88

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of the DNA-Binding domains from nfat, Fos and jun bound specifically to DNA.

Authors

L.Chen, J.N.Glover, P.G.Hogan, A.Rao, S.C.Harrison.

Ref.

Nature, 1998, 392, 42-48. [DOI no: 10.1038/32100]

PubMed id

9510247

Abstract

The nuclear factor of activated T cells (NFAT) and the AP-1 heterodimer, Fos-Jun, cooperatively bind a composite DNA site and synergistically activate the expression of many immune-response genes. A 2.7-A-resolution crystal structure of the DNA-binding domains of NFAT, Fos and Jun, in a quaternary complex with a DNA fragment containing the distal antigen-receptor response element from the interleukin-2 gene promoter, shows an extended interface between NFAT and AP-1, facilitated by the bending of Fos and DNA. The tight association of the three proteins on DNA creates a continuous groove for the recognition of 15 base pairs.

Figure 4.
Figure 4 DNA recognition in the NFAT-AP-1-ARRE2 complex. a, View of the composite binding groove generated by the DNA-facing surfaces of NFAT, Fos and Jun. The colour scheme indicates electrostatic potential (blue, positive; red, negative) as calculated by the program GRASP49. b, Schematic diagram of detailed protein-DNA contacts, compared with similar contacts in the NF- B p50-DNA complex (upper left)24 and in the ternary Fos-Jun-AP-1 site complex (lower right)31. Lines with arrowheads, hydrogen bonds; lines with filled circles at either end, van der Waals contacts; solid lines, major-groove and sugar-phosphate interactions; dashed lines, minor-groove interactions. The coloured blocks indicate which protein is involved. c, Detailed view (using Ribbons50) of NFAT interactions in the major groove, showing the roles of Arg 421, Glu 427, Arg 430, Gln 571 and Arg 572 in specifying base pairs. Arg 430 is supported by salt links to Glu 427, which also accepts hydrogen bonds from the main-chain NH of Tyr 424 and from N4 of Cyt 2'. The view is essentially the same as that in Fig. 2.

Figure 5.
Figure 5 The interface between NFAT and AP-1. a, Surface representation (made with GRASP) showing the partly discontinuous character of the contacts. The box indicates the region shown in detail in b. The orientation is essentially the same as in Fig. 3c. b, Detailed view (using Ribbons50) of the contacts between the E'F and CX loops of NFAT (right) and Jun and Fos (left), respectively. Note the very extensive network of hydrogen bonds and salt bridges.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 392, 42-48) copyright 1998.