Telomere binding proteins
Ming Lei group (University of Michigan)
Ming Lei's group at the University of Michigan used data
collected data at GM/CA-CAT and LS-CAT to solve structures of telomere
binding proteins that protect chromosomes and recruit other proteins to
interact with the chromosome. 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. The
investigators dissected the interactions of TRF1 and TRF2 with their shared
binding partner, TIN2, and other shelterin accessory factors. TRF1 recognizes
a short peptide of TIN2, TIN2TBM (TIN2 TRF binding motif), 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. 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. These studies reveal that TRF1 and TRF2 share a versatile protein
interaction interface that functions as a protein docking site to recruit
different factors to telomeres by specifically interacting with either TRF1
or TRF2.
 |
Figure: Crystal Structure of TRF2 TRFH domain and TIN2 peptide complex [PDB ID 3BU8] |
Citation:
Chen, Y, Yang, Y, van Overbeek, M, Donigian, JR, Baciu, P, de Lange, T, Lei,
M. A Shared Docking Motif in TRF1 and TRF2 Used for Differential Recruitment
of Telomeric Proteins, Science 22, 1092-1096 (2008).
DOI:10.1126/science.1151804.
|