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PDBsum entry 2kn6
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References listed in PDB file
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Key reference
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Title
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Structure and interdomain dynamics of apoptosis-Associated speck-Like protein containing a card (asc).
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Author
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E.De alba.
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Ref.
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J Biol Chem, 2009,
284,
32932-32941.
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PubMed id
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Abstract
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The human protein ASC is a key mediator in apoptosis and inflammation. Through
its two death domains (pyrin and CARD) ASC interacts with cell death
executioners, acts as an essential adapter for inflammasome integrity, and
oligomerizes into functional supramolecular assemblies. However, these functions
are not understood at the structural-dynamic level. This study reports the
solution structure and interdomain dynamics of full-length ASC. The pyrin and
CARD domains are structurally independent six-helix bundle motifs connected by a
23-residue linker. The CARD structure reveals two distinctive characteristics;
helix 1 is not fragmented as in all other known CARDs, and its electrostatic
surface shows a uniform distribution of positive and negative charges, whereas
these are commonly separated into two areas in other death domains. The linker
adopts residual structure resulting in a back-to-back orientation of the
domains, which avoids steric interference of each domain with the binding site
of the other. NMR relaxation experiments show that the linker is flexible
despite the residual structure. This flexibility could help expand the relative
volume occupied by each domain, thus increasing the capture radius for
effectors. Based on the ASC structure, a tentative model is proposed to
illustrate how ASC oligomerizes via CARD and pyrin homophilic interactions.
Moreover, ASC oligomers have been analyzed by atomic force microscopy, showing a
predominant species of disk-like particles of approximately 12-nm diameter and
approximately 1-nm height. Taken together, these results provide structural
insight into the behavior of ASC as an adapter molecule.
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Secondary reference #1
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Title
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1h, 15n and 13c backbone and side chain chemical shifts of human asc (apoptosis-Associated speck-Like protein containing a card domain).
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Author
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E.De alba.
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Ref.
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Biomol Nmr Assign, 2007,
1,
135-137.
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PubMed id
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