PDBsum entry 1fex

Structural protein

PDB id: 1fex

Contents

Protein chain

59 a.a. *

* Residue conservation analysis

PDB id:

1fex

Name:

Structural protein

Title:

Solution structure of myb-domain of human rap1

Structure:

Trf2-interacting telomeric rap1 protein. Chain: a. Fragment: myb-domain. Engineered: yes. Mutation: yes

Source:

Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence of this peptide occurs naturally in humans (homo sapiens).

NMR struc:

25 models

Authors:

S.Hanaoka,Y.Nishimura,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

S.Hanaoka et al. (2001). NMR structure of the hRap1 Myb motif reveals a canonical three-helix bundle lacking the positive surface charge typical of Myb DNA-binding domains. J Mol Biol, 312, 167-175. PubMed id: 11545594 DOI: 10.1006/jmbi.2001.4924

Date:

24-Jul-00 Release date: 19-Sep-01

Protein chain

Q9NYB0  (TE2IP_HUMAN) -  Telomeric repeat-binding factor 2-interacting protein 1 from Homo sapiens

Seq: 399 a.a.

Struc: 59 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1006/jmbi.2001.4924

J Mol Biol 312:167-175 (2001)

PubMed id: 11545594

NMR structure of the hRap1 Myb motif reveals a canonical three-helix bundle lacking the positive surface charge typical of Myb DNA-binding domains.

S.Hanaoka, A.Nagadoi, S.Yoshimura, S.Aimoto, B.Li, T.de Lange, Y.Nishimura.

ABSTRACT

Mammalian telomeres are composed of long tandem arrays of double-stranded telomeric TTAGGG repeats associated with the telomeric DNA-binding proteins, TRF1 and TRF2. TRF1 and TRF2 contain a similar C-terminal Myb domain that mediates sequence-specific binding to telomeric DNA. In the budding yeast, telomeric DNA is associated with scRap1p, which has a central DNA-binding domain that contains two structurally related Myb domains connected by a long linker, an N-terminal BRCT domain, and a C-terminal RCT domain. Recently, the human ortholog of scRap1p (hRap1) was identified and shown to contain a BRCT domain and an RCT domain similar to scRap1p. However, hRap1 contained only one recognizable Myb motif in the center of the protein. Furthermore, while scRap1p binds telomeric DNA directly, hRap1 has no DNA-binding ability. Instead, hRap1 is tethered to telomeres by TRF2. Here, we have determined the solution structure of the Myb domain of hRap1 by NMR. It contains three helices maintained by a hydrophobic core. The architecture of the hRap1 Myb domain is very close to that of each of the Myb domains from TRF1, scRap1p and c-Myb. However, the electrostatic potential surface of the hRap1 Myb domain is distinguished from that of the other Myb domains. Each of the minimal DNA-binding domains, containing one Myb domain in TRF1 and two Myb domains in scRap1p and c-Myb, exhibits a positively charged broad surface that contacts closely the negatively charged backbone of DNA. By contrast, the hRap1 Myb domain shows no distinct positive surface, explaining its lack of DNA-binding activity. The hRap1 Myb domain may be a member of a second class of Myb motifs that lacks DNA-binding activity but may interact instead with other proteins. Other possible members of this class are the c-Myb R1 Myb domain and the Myb domains of ADA2 and Adf1. Thus, while the folds of all Myb domains resemble each other closely, the function of each Myb domain depends on the amino acid residues that are located on the surface of each protein.

Selected figure(s)

Figure 2.
Figure 2. NOE connectivities of the hRap1 Myb domain. Boxed and gray regions are helical regions.

Figure 3.
Figure 3. Stereoviews of the Myb domain structure of hRap1. (a) A stereoview of the 25 superimposed structures with amino acid residues that form a hydrophobic core of the Myb domain of hRap1. Cyan-colored residues form a hydrophobic core, maintaining the architecture of the three helices. (b) A stereoview of the lowest-energy structure in the 25 structures of the Myb domain of hRap1. Amino acid residues that form a hydrophobic core are indicated.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 312, 167-175) copyright 2001.

Figures were selected by an automated process.