Nuclear localization signal protein binding

Figure 2. Structural and functional domains of PARP-1. PARP-1 has a highly conserved structural and functional organization including (1) an N-terminal DNA binding domain with two Cys-Cys-His-Cys zinc finger motifs (FI and Fll), (2) a nuclear localization signal (NLS), (3) a central automodification domain containing a BRCT ( BRCAl C-terminus-like ) protein-protein interaction motif, and (4) a C-terminal catalytic domain with a contiguous 50 amino acid sequence, the PARP signature motif, that forms the active site...

A typical nuclear receptor contains a domain responsible for the DNA binding (domain C), the ligand binding and dimerization (E), and for the transactivation and other protein-protein interactions (A,B,E,F). Furthermore, there are also nuclear localization signals (D). 

Fig. 10.8 Above, import of the transcription factor NF-AT4 into the nucleus. In activated cells, import is initiated by calcineurin-mediated dephosphorylation of NF-AT4. Dephosphorylation unmasks the nuclear-localization signal (NLS), and at the same time blocks the nuclear export signal (NES). The NES is recognized by the exportin protein (Crml). Nuclear export is an active process. Moreover, nuclear export requires rephosphorylation of the NF-AT4 transcription factor. It is indicated that dephosphorylation by calcineurin and nuclear export are mutually exclusive, because calcineurin and Crm 1 compete for a common binding site on NES. When NES binds to Crml, NT-AT4 is exported from the nucleus, and when calcineurin binds to NES, NF-AT4 remains in the nucleus and forms a transcriptionally active complex. Below, how the extent of dephosphorylation controls the transcriptional activity of NF-AT4. When NF-AT4 is fully phosphorylated, NLS is hidden and the transcription factor remains in the cytoplasm. When NF-AT4 is only partially dephosphorylated, NLS is exposed and can interact with importin a/b which promote nuclear import, and at the same time, NES can interact with the exportin Crml, which promotes nuclear export. The consequence is that the transcription factor shuttles between the nucleus and the cytoplasm and is not transcriptionally active. In order to become transcriptionally fully active, NF-AT4 must be completely dephosphorylated. This prevents export from the nucleus by blocking NES, and may increase the affinity of the transcription factor for DNA by exposure of its trans-activating domain (TAD). (The entire scheme is reproduced with permission of Drs Patrick G. Hogan and Anjana Rao and Nature from Fig. 1 in ref. 68.)...

Figure 12.39. Protein Targeting Signal Recognition. The structure of the nuclear localization signal-binding protein a-karyopherin (also known as a-importin) with a nuclear localization signal peptide bound to its major recognition...

The complex structure is a distinctive feature of Abl tyrosine kinase (Fig. 8.18). The enzyme possesses a Tyr kinase domain, an SH2 and an SH3 domain, three nuclear localization signals, a DNA-binding domain, binding domains for microfilament proteins, namely G-actin and F-actin, and a C-terminal myristinic acid residue as a membrane anchor. It is autophosphorylated and phosphorylated by other protein kinases, c-... 

LaCasse, E. C., and Y. A. Lefebvre. 1995. Nuclear localization signals overlap DNA-or RNA-binding domains in nucleic acid-binding proteins. Nucleic Acids Res 23 1647-56. 

As depicted in Figure 14-2, R-Smads contain two domains, MHl and MH2, separated by a flexible linker region. The N-terminal MHl domain contains the specific DNA-blndlng segment and also a sequence called the nuclear-localization signal (NLS) that is required for protein transport into the nucleus (Chapter 12). When R-Smads are in their inactive, nonphosphorylated state, the NLS is masked and the MHl and MH2 domains associate in such a way that they cannot bind to DNA or to a co-Smad. Phosphorylation of three serine residues near the C-terminus of an R-Smad (Smad2 or Smad3) by activated type I TGF(3 re-... 

---