3SIQ

Crystal Structure of autoinhibited dIAP1-BIR1 domain

Summary for 3SIQ

• Entry DOI: 10.2210/pdb3siq/pdb
• Related: 3SIP
• Descriptor: Apoptosis 1 inhibitor, ZINC ION (3 entities in total)
• Functional Keywords: diap1-bir1 domain, ligase
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 6
• Total formula weight: 96373.98

Authors

Li, X.,Wang, J.,Shi, Y. (deposition date: 2011-06-20, release date: 2011-08-10, Last modification date: 2023-11-01)

Primary citation

Li, X.,Wang, J.,Shi, Y.
Structural mechanisms of DIAP1 auto-inhibition and DIAP1-mediated inhibition of drICE.
Nat Commun, 2:408-408, 2011

PubMed Abstract: The Drosophila inhibitor of apoptosis protein DIAP1 exists in an auto-inhibited conformation, unable to suppress the effector caspase drICE. Auto-inhibition is disabled by caspase-mediated cleavage of DIAP1 after Asp20. The cleaved DIAP1 binds to mature drICE, inhibits its protease activity, and, presumably, also targets drICE for ubiquitylation. DIAP1-mediated suppression of drICE is effectively antagonized by the pro-apoptotic proteins Reaper, Hid, and Grim (RHG). Despite rigorous effort, the molecular mechanisms behind these observations are enigmatic. Here we report a 2.4 Å crystal structure of uncleaved DIAP1-BIR1, which reveals how the amino-terminal sequences recognize a conserved surface groove in BIR1 to achieve auto-inhibition, and a 3.5 Å crystal structure of active drICE bound to cleaved DIAP1-BIR1, which provides a structural explanation to DIAP1-mediated inhibition of drICE. These structures and associated biochemical analyses, together with published reports, define the molecular determinants that govern the interplay among DIAP1, drICE and the RHG proteins.

PubMed: 21811237
DOI: 10.1038/ncomms1418

Experimental method

X-RAY DIFFRACTION (2.4 Å)