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2LB3

Structure of the WW domain of PIN1 in complex with a human phosphorylated Smad3 derived peptide

Summary for 2LB3
Entry DOI10.2210/pdb2lb3/pdb
Related2LAW 2LAX 2LAY 2LAZ 2LB0 2LB1 2LB2
NMR InformationBMRB: 17545
DescriptorPeptidyl-prolyl cis-trans isomerase NIMA-interacting 1, Mothers against decapentaplegic homolog 2 (2 entities in total)
Functional Keywordspin1, smad, cdk, signal transduction, signaling protein-transcription complex, signaling protein/transcription
Biological sourceHomo sapiens (human)
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Cellular locationNucleus: Q13526
Cytoplasm: Q15796
Total number of polymer chains2
Total formula weight5118.57
Authors
Macias, M.J.,Aragon, E.,Goerner, N.,Zaromytidou, A.,Xi, Q.,Escobedo, A.,Massague, J. (deposition date: 2011-03-22, release date: 2011-07-06, Last modification date: 2024-11-06)
Primary citationAragon, E.,Goerner, N.,Zaromytidou, A.I.,Xi, Q.,Escobedo, A.,Massague, J.,Macias, M.J.
A Smad action turnover switch operated by WW domain readers of a phosphoserine code.
Genes Dev., 25:1275-1288, 2011
Cited by
PubMed Abstract: When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen synthase kinase-3 (GSK3) phosphorylations that mediate the binding of YAP and Pin1 for transcriptional action, and of ubiquitin ligases Smurf1 and Nedd4L for Smad destruction. Here we demonstrate that there is an order of events-Smad activation first and destruction later-and that it is controlled by a switch in the recognition of Smad phosphoserines by WW domains in their binding partners. In the BMP pathway, Smad1 phosphorylation by CDK8/9 creates binding sites for the WW domains of YAP, and subsequent phosphorylation by GSK3 switches off YAP binding and adds binding sites for Smurf1 WW domains. Similarly, in the TGF-β pathway, Smad3 phosphorylation by CDK8/9 creates binding sites for Pin1 and GSK3, then adds sites to enhance Nedd4L binding. Thus, a Smad phosphoserine code and a set of WW domain code readers provide an efficient solution to the problem of coupling TGF-β signal delivery to turnover of the Smad signal transducers.
PubMed: 21685363
DOI: 10.1101/gad.2060811
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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