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Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.

ABSTRACT: Prp8 stands out among hundreds of splicing factors as a key regulator of spliceosome activation and a potential cofactor of the splicing reaction. We present here the crystal structure of a 274-residue domain (residues 1,822-2,095) near the C terminus of Saccharomyces cerevisiae Prp8. The most striking feature of this domain is a beta-hairpin finger protruding out of the protein (hence, this domain will be referred to as the beta-finger domain), resembling many globular ribosomal proteins with protruding extensions. Mutations throughout the beta-finger change the conformational equilibrium between the first and the second catalytic step. Mutations at the base of the beta-finger affect U4/U6 unwinding-mediated spliceosome activation. Prp8 may insert its beta-finger into the first-step complex (U2/U5/U6/pre-mRNA) or U4/U6.U5 tri-snRNP and stabilize these complexes. Mutations on the beta-finger likely alter these interactions, leading to the observed mutant phenotypes. Our results suggest a possible mechanism of how Prp8 regulates spliceosome activation. These results also demonstrate an analogy between a spliceosomal protein and ribosomal proteins that insert extensions into folded rRNAs and stabilize the ribosome.

SUBMITTER: Yang K

PROVIDER: S-EPMC2544537 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.

Yang Kui K Zhang Lingdi L Xu Tao T Heroux Annie A Zhao Rui R

Proceedings of the National Academy of Sciences of the United States of America 20080908 37

Prp8 stands out among hundreds of splicing factors as a key regulator of spliceosome activation and a potential cofactor of the splicing reaction. We present here the crystal structure of a 274-residue domain (residues 1,822-2,095) near the C terminus of Saccharomyces cerevisiae Prp8. The most striking feature of this domain is a beta-hairpin finger protruding out of the protein (hence, this domain will be referred to as the beta-finger domain), resembling many globular ribosomal proteins with p ...[more]

PMID: 18779563

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Project description:Epidermal cells of dark-grown plant seedlings reorient their cortical microtubule arrays in response to blue light from a net lateral orientation to a net longitudinal orientation with respect to the long axis of cells. The molecular mechanism underlying this microtubule array reorientation involves katanin, a microtubule severing enzyme, and a plant-specific microtubule associated protein called SPIRAL2. Katanin preferentially severs longitudinal microtubules, generating seeds that amplify the longitudinal array. Upon severing, SPIRAL2 binds nascent microtubule minus ends and limits their dynamics, thereby stabilizing the longitudinal array while the lateral array undergoes net depolymerization. To date, no experimental structural information is available for SPIRAL2 to help inform its mechanism. To gain insight into SPIRAL2 structure and function, we determined a 1.8 Å resolution crystal structure of the Arabidopsis thaliana SPIRAL2 C-terminal domain. The domain is composed of seven core α-helices, arranged in an α-solenoid. Amino-acid sequence conservation maps primarily to one face of the domain involving helices α1, α3, α5, and an extended loop, the α6-α7 loop. The domain fold is similar to, yet structurally distinct from the C-terminal domain of Ge-1 (an mRNA decapping complex factor involved in P-body localization) and, surprisingly, the C-terminal domain of the katanin p80 regulatory subunit. The katanin p80 C-terminal domain heterodimerizes with the MIT domain of the katanin p60 catalytic subunit, and in metazoans, binds the microtubule minus-end factors CAMSAP3 and ASPM. Structural analysis predicts that SPIRAL2 does not engage katanin p60 in a mode homologous to katanin p80. The SPIRAL2 structure highlights an interesting evolutionary convergence of domain architecture and microtubule minus-end localization between SPIRAL2 and katanin complexes, and establishes a foundation upon which structure-function analysis can be conducted to elucidate the role of this domain in the regulation of plant microtubule arrays.

Dataset Information

Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.

Publications

Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins.

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