PDBsum entry 1ucp

Apoptosis

PDB id: 1ucp

Contents

Protein chain

91 a.a. *

* Residue conservation analysis

References listed in PDB file

Key reference

Title

The death-Domain fold of the asc pyrin domain, Presenting a basis for pyrin/pyrin recognition.

Authors

E.Liepinsh, R.Barbals, E.Dahl, A.Sharipo, E.Staub, G.Otting.

Ref.

J Mol Biol, 2003, 332, 1155-1163. [DOI no: 10.1016/j.jmb.2003.07.007]

PubMed id

14499617

Abstract

The PYRIN domain is a conserved sequence motif identified in more than 20 human proteins with putative functions in apoptotic and inflammatory signalling pathways. The three-dimensional structure of the PYRIN domain from human ASC was determined by NMR spectroscopy. The structure determination reveals close structural similarity to death domains, death effector domains, and caspase activation and recruitment domains, although the structural alignment with these other members of the death-domain superfamily differs from previously predicted amino acid sequence alignments. Two highly positively and negatively charged surfaces in the PYRIN domain of ASC result in a strong electrostatic dipole moment that is predicted to be present also in related PYRIN domains. These results suggest that electrostatic interactions play an important role for the binding between PYRIN domains. Consequently, the previously reported binding between the PYRIN domains of ASC and ASC2/POP1 or between the zebrafish PYRIN domains of zAsc and Caspy is proposed to involve interactions between helices 2 and 3 of one PYRIN domain with helices 1 and 4 of the other PYRIN domain, in analogy to previously reported homophilic interactions between caspase activation and recruitment domains.

Figure 3.
Figure 3. Amino acid sequence alignment of PYRIN domains, PYRIN domain structure and distribution of charged residues. A, Amino acid sequence alignment of 35 PYRIN domains from human and mouse and two from zebrafish. The PYRIN domain of ASC is shown at the top, together with its sequence numbering. The amino acid sequence of the FADD DED domain is shown at the bottom for comparison. The location of the helices and buried side-chains with less than 5% solvent exposure is indicated for the ASC PYRIN domain and the FADD DED domain by bars and filled squares, respectively. Arrows identify positions of significant differences between the PYRIN domains and the DED consensus. The consensus sequence of PYRIN domains is indicated below the PYRIN sequences, where upper case letters indicate conservation of distinct amino acids and lower case letters indicate conservation of (h)ydrophobic, (c)harged, (p)olar, a(l)iphatic, and (t)iny amino acid side-chains. Consensus characters were assigned when >80% of the residues of a column belong to the same amino acid class. hs, Homo sapiens; mm, Mus musculus; PYRIN, pyrin protein; z, zebrafish; ASC, apoptosis-associated speck-like protein containing a CARD; POP1, pyrin-only protein 1; CIAS1, cold autoinflammatory syndrome 1 (also called PYPAF1 or cryopyrin); CRYOPYR_11, cryopyrin-like protein 1; NALP2, NACHT-, LRR-, and PYD-containing protein 2 (also called PYPAF2); NLP2_l1, NALP2-like protein 1; NLP3_l1, NALP3-like protein 1; PYPAF1-7: PYRIN-containing APAF1-like protein 1-7; PYPAF4_l1-3, PYPAF4 like proteins 1, 2 and 3; DEFCAP, death effector filament-forming Ced-4-like apoptosis protein; IFI16, interferon gamma-inducible protein 16; IFI16_l1-2, IFI16-like proteins 1 and 2; IFI203 and IFI204, interferon-activatable proteins 203 and 204; MNDA, myeloid cell nuclear differentiation antigen; AIM2, absent in melanoma 2; MATER, maternal-antigen-that-embryos-require; ANGIN2_l1-3, angiogenin inhibitor 2-like proteins 1-3; MCMI1, mast cell maturation-inducible protein-like protein; DKFZ, predicted protein from DKFZ institute transcript; ENSMUSP00000038294 and ENSMUSP00000048095: hypothetical proteins predicted by the ENSEMBL genome annotation project. hs_POP1 is also called ASC2.[30. and 46.]

Figure 4.
Figure 4. PYRIN domain structure and distribution of charged residues. (a) Stereo view of a superposition of the backbone atoms in the 20 conformers representing the NMR structure of the ASC PYRIN domain (Table 1). Numbers identify sequence positions. (b) Stereo view of the conformer closest to the mean structure of the 20 conformers shown in (a). The following colors were used for the side-chains: blue, Arg, Lys, His; red, Glu, Asp; yellow, Ala, Cys, Ile, Leu, Met, Phe, Pro, Trp, Val; grey, Asn, Gln, Ser, Thr, Tyr. Bold lines identify charged side-chains of Arg, Lys, Asp and Glu. The molecule is oriented so that most of the negatively and positively charged side chains are located, respectively, in the left and right half of the molecule. (c) and (d) Ribbon drawing of the PYRIN domain. Spheres identify the positions of C^a atoms, where positively (blue) and negatively (red) charged side-chains are located in the zebrafisch PYRIN domains of zAsc (c) and Caspy (d). The six helices are numbered.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 332, 1155-1163) copyright 2003.