7S1O

Structure of human POT1C

Summary for 7S1O

• Entry DOI: 10.2210/pdb7s1o/pdb
• Descriptor: Protection of telomeres protein 1, ZINC ION (3 entities in total)
• Functional Keywords: pot1, telomere, dna binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 71024.27

Authors

Aramburu, T.,Skordalakes, E. (deposition date: 2021-09-02, release date: 2022-01-19, Last modification date: 2023-10-18)

Primary citation

Aramburu, T.,Kelich, J.,Rice, C.,Skordalakes, E.
POT1-TPP1 binding stabilizes POT1, promoting efficient telomere maintenance.
Comput Struct Biotechnol J, 20:675-684, 2022

PubMed Abstract: Telomeric POT1-TPP1 binding is critical to telomere maintenance and disruption of this complex may lead to cancer. Current data suggests a reduction of intracellular POT1 levels in the absence of TPP1. Here we provide evidence of POT1 plasticity that contributes to its lack of stability in the absence of TPP1 binding. Structural data reveals inter- and intramolecular POT1C domain flexibility in the absence of TPP1. Thermostability and proteolytic resistance assays show that POT1C and the mutant complex POT1C(Q623H)-TPP1(PBD) are less stable than the wild type POT1C-TPP1(PBD), suggesting that TPP1 binding to POT1 stabilizes POT1C and makes it less accessible to proteasomal degradation in the cell. Disruption of the POT1-TPP1 complex such as through cancer-associated mutations leads to a reduction of intracellular POT1, telomere uncapping, and telomere associated DNA damage response (DDR). DDR in turn leads to senescence or genomic instability and oncogenesis.

PubMed: 35140887
DOI: 10.1016/j.csbj.2022.01.005

Experimental method

X-RAY DIFFRACTION (2.55 Å)