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Metal binding sheds light on mechanisms of amyloid assembly.

ABSTRACT: Beta-2 microglobulin (beta2m) is the protein responsible for amyloid deposition in Dialysis-Related Amyloidosis (DRA). Aggregation can be induced by various solution conditions including exposure to divalent metal, incubation at acidic pH, and limited proteolysis. Using Cu(2+) as a trigger, we have trapped, isolated, and crystallized a stable oligomer of beta2m that is populated under amyloidogenic solution conditions (Calabrese et al. Nat Struct Mol Biol 2008; 15:965-71). This structure reveals that Cu(2+)-binding is associated with dramatic conformational rearrangements. This has allowed us to postulate a set of structural changes common to all beta2m aggregation pathways. Cu(2+) serves as a potential trigger in other aggregation systems such as Abeta, alpha-synuclein, and mammalian Prion (PrP). A comparison of Cu(2+) binding to beta2m and PrP reveals common features. Therefore, in addition to providing insight into DRA, induction of structure by Cu(2+) binding appears to be a recurring structural motif for pathological changes in conformation.

SUBMITTER: Calabrese MF

PROVIDER: S-EPMC2676736 | biostudies-literature | 2009 Jan-Mar

REPOSITORIES: biostudies-literature

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Metal binding sheds light on mechanisms of amyloid assembly.

Calabrese Matthew F MF Miranker Andrew D AD

Prion 20090128 1

Beta-2 microglobulin (beta2m) is the protein responsible for amyloid deposition in Dialysis-Related Amyloidosis (DRA). Aggregation can be induced by various solution conditions including exposure to divalent metal, incubation at acidic pH, and limited proteolysis. Using Cu(2+) as a trigger, we have trapped, isolated, and crystallized a stable oligomer of beta2m that is populated under amyloidogenic solution conditions (Calabrese et al. Nat Struct Mol Biol 2008; 15:965-71). This structure reveals ...[more]

PMID: 19377278

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Project description:BackgroundMurraya paniculata (L.) Jack, commonly called orange jessamine in the family Rutaceae, is an important ornamental plant in tropical and subtropical regions which is famous for its strong fragrance. Although genome assemblies have been reported for many Rutaceae species, mainly in the genus Citrus, full genomic information has not been reported for M. paniculata, which is a prerequisite for in-depth genetic studies on Murraya and manipulation using genetic engineering techniques. Here, we report a high-quality chromosome-level genome assembly of M. paniculata and aim to provide insights on the molecular mechanisms of flower volatile biosynthesis.ResultsThe genome assembly with a contig N50 of 18.25 Mb consists of 9 pseudomolecules and has a total length of 216.86 Mb. Phylogenetic analysis revealed that M. paniculata diverged from the common ancestor approximately 25 million years ago and has not undergone any species-specific whole genome duplication events. Genome structural annotation and comparative genomics analysis revealed that there are obvious differences in transposon contents among the genomes of M. paniculata and Citrus species, especially in the upstream regions of genes. Research on the flower volatiles of M. paniculata and C. maxima at three flowering stages revealed significant differences in volatile composition with the flowers of C. maxima lacking benzaldehyde and phenylacetaldehyde. Notably, there are transposons inserted in the upstream region of the phenylacetaldehyde synthase (PAAS) genes Cg1g029630 and Cg1g029640 in C. maxima, but not in the upstream region of three PAAS genes Me2G_2379, Me2G_2381, and Me2G_2382 in M. paniculata. Our results indicated that compared to the low expression levels of PAAS genes in C. maxima, the higher expression levels of the three PAAS genes in M. paniculata are the main factor affecting the phenylacetaldehyde biosynthesis and causing the content difference of phenylacetaldehyde. The phenylacetaldehyde synthetic activities of the enzymes encoded by M. paniculata PAAS genes were validated by in vitro analyses.ConclusionsOur study provides useful genomic resources of M. paniculata for further research on Rutaceae plants, identifies new PAAS genes, and provides insights into how transposons contribute to variations in flower volatiles among Murraya and Citrus plants.

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Metal binding sheds light on mechanisms of amyloid assembly.

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Metal binding sheds light on mechanisms of amyloid assembly.

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