PDBsum entry 3bua

DNA binding protein

PDB id: 3bua

Contents

Protein chains

202 a.a. *

14 a.a. *

12 a.a. *

16 a.a. *

12 a.a. *

Waters ×110

* Residue conservation analysis

PDB id:

3bua

Name:

DNA binding protein

Title:

Crystal structure of trf2 trfh domain and apollo peptide complex

Structure:

Telomeric repeat-binding factor 2. Chain: a, b, c, d. Fragment: trfh domain, dimerization domain. Synonym: ttaggg repeat-binding factor 2, telomeric DNA-binding protein. Engineered: yes. DNA cross-link repair 1b protein. Chain: e, f, g, h. Fragment: unp residues 495-530.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: terf2, trbf2, trf2. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: dclre1b, snm1b.

Resolution:

2.50Å R-factor: 0.229 R-free: 0.254

Authors:

Y.Chen,Y.Yang,M.Van Overbeek,J.R.Donigian,P.Baciu,T.De Lange,M.Lei

Key ref:

Y.Chen et al. (2008). A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science, 319, 1092-1096. PubMed id: 18202258 DOI: 10.1126/science.1151804

Date:

02-Jan-08 Release date: 19-Feb-08

Protein chains

Q15554  (TERF2_HUMAN) -  Telomeric repeat-binding factor 2 from Homo sapiens

Seq: 542 a.a.

Struc: 202 a.a.

Protein chain

Q9H816  (DCR1B_HUMAN) -  5' exonuclease Apollo from Homo sapiens

Seq: 532 a.a.

Struc: 14 a.a.

Protein chain

Q9H816  (DCR1B_HUMAN) -  5' exonuclease Apollo from Homo sapiens

Seq: 532 a.a.

Struc: 12 a.a.

Protein chain

Q9H816  (DCR1B_HUMAN) -  5' exonuclease Apollo from Homo sapiens

Seq: 532 a.a.

Struc: 16 a.a.*

Protein chain

Q9H816  (DCR1B_HUMAN) -  5' exonuclease Apollo from Homo sapiens

Seq: 532 a.a.

Struc: 12 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D: E.C.?
• Enzyme class 3: Chains E, F, G, H: E.C.3.1.-.-
• Enzyme class 4: Chains E, F, G, H: E.C.3.5.2.6 - beta-lactamase.

Pathway:

• Reaction: a beta-lactam + H2O = a substituted beta-amino acid
• Cofactor: Zn(2+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1126/science.1151804

Science 319:1092-1096 (2008)

PubMed id: 18202258

A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins.

Y.Chen, Y.Yang, M.van Overbeek, J.R.Donigian, P.Baciu, T.de Lange, M.Lei.

ABSTRACT

Mammalian telomeres are protected by a six-protein complex: shelterin. Shelterin contains two closely related proteins (TRF1 and TRF2), which recruit various proteins to telomeres. We dissect the interactions of TRF1 and TRF2 with their shared binding partner (TIN2) and other shelterin accessory factors. TRF1 recognizes TIN2 using a conserved molecular surface in its TRF homology (TRFH) domain. However, this same surface does not act as a TIN2 binding site in TRF2, and TIN2 binding to TRF2 is mediated by a region outside the TRFH domain. Instead, the TRFH docking site of TRF2 binds a shelterin accessory factor (Apollo), which does not interact with the TRFH domain of TRF1. Conversely, the TRFH domain of TRF1, but not of TRF2, interacts with another shelterin-associated factor: PinX1.

Selected figure(s)

Figure 3.
Fig. 3. The TRF2-TIN2 interaction. (A) Co-IP of TIN2 with cotransfected wild-type and mutant TRF2. (B) Far-Western analysis of the TIN2 binding region of TRF2 (FL, full-length; TRF2- B, TRF2- 1–42). (C) Superposition of the TIN2[TBM] binding sites in the TRF1[TRFH]-TIN2[TBM] and TRF2[TRFH]-TIN2[TBM] complexes. TRF1[TRFH] and TRF2[TRFH] are in green and cyan, respectively. The TIN2[TBM] peptides bound to TRF1[TRFH] and TRF2[TRFH]are shown in stick model format and in yellow and magenta, respectively. (D) TIN2-F258 interacts less efficiently with TRF2 than with TRF1. The F258 binding surfaces of TRF1[TRFH] (top panel) and TRF2[TRFH] (bottom panel) are shown in magenta (hydrophobic patch) and blue (hydrophilic patch). The rest of TRF1[TRFH] and TRF2[TRFH] is in green and cyan, respectively.

Figure 4.
Fig. 4. The TRF2-Apollo interaction. (A) ITC measurement of the interactions of TRF1[TRFH] (red) and TRF2[TRFH] (blue) with the Apollo[TBM] peptide. (B) Overall structure of the dimeric TRF2[TRFH]-Apollo[TBM] complex. (C) Superposition of Apollo[TBM] (orange) and TIN2[TBM] (yellow) reveals a shared F/Y-X-L-X-P motif. (D) Superposition of the TRF2[TRFH]-Apollo[TBM] and the TRF2[TRFH]-TIN2[TBM] complexes in the vicinity of the Apollo helix. The TRF2[TRFH] molecules are colored in cyan (Apollo[TBM]-bound) and gray (TIN2[TBM]-bound), respectively. (E) Apollo[TBM] binding is TRF2[TRFH]-specific. The surface representations show that there is no room for Apollo L500 and Y504 to fit into the peptide binding site of TRF1[TRFH]. (F) In vitro ITC binding data of wild-type and mutant TRF2[TRFH]-Apollo[TBM] interactions. (G) Co-IP data show that Apollo double-mutant L504E/P506 and TRF2 single-mutant F120A disrupt the in vivo TRF2-Apollo interaction. (H) Localization of retrovirally expressed HA-tagged wild type and L506E/P508A double mutant of Apollo in BJ-hTERT cells.

The above figures are reprinted by permission from the AAAs: Science (2008, 319, 1092-1096) copyright 2008.

Figures were selected by an automated process.