5KNI

Crystal Structure of the wild-type SAM domain of human Tankyrase-1

Summary for 5KNI

• Entry DOI: 10.2210/pdb5kni/pdb
• Descriptor: Tankyrase-1 (2 entities in total)
• Functional Keywords: tankyrase, sterile alpha motif sam domain, tnks, tnks1, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 7
• Total formula weight: 52973.46

Authors

Pascal, J.M.,McCauley, M.,Langelier, M.F.,Riccio, A.A. (deposition date: 2016-06-28, release date: 2016-08-31, Last modification date: 2023-09-27)

Primary citation

Riccio, A.A.,McCauley, M.,Langelier, M.F.,Pascal, J.M.
Tankyrase Sterile alpha Motif Domain Polymerization Is Required for Its Role in Wnt Signaling.
Structure, 24:1573-1581, 2016

PubMed Abstract: Tankyrase-1 (TNKS1/PARP-5a) is a poly(ADP-ribose) polymerase (PARP) enzyme that regulates multiple cellular processes creating a poly(ADP-ribose) posttranslational modification that can lead to target protein turnover. TNKS1 thereby controls protein levels of key components of signaling pathways, including Axin1, the limiting component of the destruction complex in canonical Wnt signaling that degrades β-catenin to prevent its coactivator function in gene expression. There are limited molecular level insights into TNKS1 regulation in cell signaling pathways. TNKS1 has a sterile α motif (SAM) domain that is known to mediate polymerization, but the functional requirement for SAM polymerization has not been assessed. We have determined the crystal structure of wild-type human TNKS1 SAM domain and used structure-based mutagenesis to disrupt polymer formation and assess the consequences on TNKS1 regulation of β-catenin-dependent transcription. Our data indicate the SAM polymer is critical for TNKS1 catalytic activity and allows TNKS1 to efficiently access cytoplasmic signaling complexes.

PubMed: 27499439
DOI: 10.1016/j.str.2016.06.022

Experimental method

X-RAY DIFFRACTION (2.5 Å)