5WIR

Structure of the TRF1-TERB1 interface

Summary for 5WIR

• Entry DOI: 10.2210/pdb5wir/pdb
• Descriptor: TERB1-TBM, Telomeric repeat-binding factor 1 (3 entities in total)
• Functional Keywords: meiosis, telomere, cdk phosphorylation, dna binding protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 50544.24

Authors

Nandakumar, J.,Pendlebury, D.F.,Smith, E.M.,Tesmer, V.M. (deposition date: 2017-07-20, release date: 2017-10-18, Last modification date: 2023-10-04)

Primary citation

Pendlebury, D.F.,Fujiwara, Y.,Tesmer, V.M.,Smith, E.M.,Shibuya, H.,Watanabe, Y.,Nandakumar, J.
Dissecting the telomere-inner nuclear membrane interface formed in meiosis.
Nat. Struct. Mol. Biol., 24:1064-1072, 2017

PubMed Abstract: Tethering telomeres to the inner nuclear membrane (INM) allows homologous chromosome pairing during meiosis. The meiosis-specific protein TERB1 binds the telomeric protein TRF1 to establish telomere-INM connectivity and is essential for mouse fertility. Here we solve the structure of the human TRF1-TERB1 interface to reveal the structural basis for telomere-INM linkage. Disruption of this interface abrogates binding and compromises telomere-INM attachment in mice. An embedded CDK-phosphorylation site within the TRF1-binding region of TERB1 provides a mechanism for cap exchange, a late-pachytene phenomenon involving the dissociation of the TRF1-TERB1 complex. Indeed, further strengthening this interaction interferes with cap exchange. Finally, our biochemical analysis implicates distinct complexes for telomere-INM tethering and chromosome-end protection during meiosis. Our studies unravel the structure, stoichiometry, and physiological implications underlying telomere-INM tethering, thereby providing unprecedented insights into the unique function of telomeres in meiosis.

PubMed: 29083414
DOI: 10.1038/nsmb.3493

Experimental method

X-RAY DIFFRACTION (2.1 Å)