2L9M

Structure of cIAP1 CARD

Summary for 2L9M

• Entry DOI: 10.2210/pdb2l9m/pdb
• NMR Information: BMRB: 17478
• Descriptor: Baculoviral IAP repeat-containing protein 2 (1 entity in total)
• Functional Keywords: card, iap, caspase, apoptosis inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (Potential): Q13490
• Total number of polymer chains: 1
• Total formula weight: 15147.40

Authors

Day, C.L.,Rautureau, G.J.P.,Hinds, M.G. (deposition date: 2011-02-21, release date: 2011-08-17, Last modification date: 2024-05-15)

Primary citation

Lopez, J.,John, S.W.,Tenev, T.,Rautureau, G.J.,Hinds, M.G.,Francalanci, F.,Wilson, R.,Broemer, M.,Santoro, M.M.,Day, C.L.,Meier, P.
CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration.
Mol.Cell, 42:569-583, 2011

PubMed Abstract: E3 ligases mediate the covalent attachment of ubiquitin to target proteins thereby enabling ubiquitin-dependent signaling. Unraveling how E3 ligases are regulated is important because miscontrolled ubiquitylation can lead to disease. Cellular inhibitor of apoptosis (cIAP) proteins are E3 ligases that modulate diverse biological processes such as cell survival, proliferation, and migration. Here, we have solved the structure of the caspase recruitment domain (CARD) of cIAP1 and identified that it is required for cIAP1 autoregulation. We demonstrate that the CARD inhibits activation of cIAP1's E3 activity by preventing RING dimerization, E2 binding, and E2 activation. Moreover, we show that the CARD is required to suppress cell proliferation and migration. Further, CARD-mediated autoregulation is also necessary to maximally suppress caspase-8-dependent apoptosis and vascular tree degeneration in vivo. Taken together, our data reveal mechanisms by which the E3 ligase activity of cIAP1 is controlled, and how its deregulation impacts on cell proliferation, migration and cell survival.

PubMed: 21549626
DOI: 10.1016/j.molcel.2011.04.008

Experimental method

SOLUTION NMR