A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins.
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.
Chen
Yong
Y
Department of Biological Chemistry, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
Yang
Yuting
Y
van Overbeek
Megan
M
Donigian
Jill R
JR
Baciu
Paul
P
de Lange
Titia
T
Lei
Ming
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D051034:Inhibitor of Apoptosis Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry* / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism
C401541:BIRC6 protein, human; D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; D050505:Mutant Proteins; D009687:Nuclear Proteins; C440808:PINX1 protein, human; D000089804:Shelterin Complex; D035182:TATA Box Binding Protein-Like Proteins; C504753:TERF2 protein, human; C440868:TINF2 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D025521:Tumor Suppressor Proteins