The (beta/alpha)(8)-barrel domain consists of eight topologically equivalent supersecondary structural motifs known as beta/alpha-units. Each unit consists of a single beta-strand, an alpha-helix, and two loops. Evidence collected in recent years indicates that the (beta/alpha)(8)-barrel motif may not be a single, autonomously-folding domain, as was previously assumed. Segments of some (beta/alpha)(8)-barrels appear to fold autonomously. However, the extent to which this is true of various (beta/alpha)(8)-barrel domains remains to be explored. In this study, we have scrambled (reshuffled) the native order of beta/alpha-units (1-2-3-4-5-6-7-8) comprising the polypeptide chain of a model (beta/alpha)(8)-barrel from S. cerevisiae, triosephosphate isomerase (TIM). Total scrambling was effected in order to examine whether folding can still occur to yield beta/alpha-structures in spite of a global 'destruction' of native hydrophobic and hydrogen bonding interactions among beta/alpha-units, while still allowing the occurrence of native interactions within individual units. Our results demonstrate that scrambled full-barrel forms (2-4-6-8-1-3-5-7 and 1-3-5-7-2-4-6-8), as well as half-barrel (2-4-6-8) and quarter-barrel (1-3) forms of TIM fold into beta/alpha-structures that sustain tertiary and quaternary structural interactions. In particular, one variant (2-4-6-8-1-3-5-7) was found to fold and form a stable dimer with native-like structural content and other characteristics. Our results demonstrate that (beta/alpha)(8)-barrels can tolerate profound alterations of both strand-strand interactions responsible for the creation of the beta-barrel and the geometry of presentation of nonpolar sidechains into the hydrophobic core of the beta-barrel by individual beta-strands. These findings lend support to our recent proposal1 that a hierarchy of interactions probably regulates structure formation and stability in (beta/alpha)(8)-barrels, where folding proceeds successively through three stages: (i) the tentative formation of individual beta/alpha-units which associate through 'near-neighbor' diffusion-collision interactions into (ii) curved assemblies of multiple beta/alpha-units through sequence-independent hydrogen bonding of strands of neighboring units, leading finally to (iii) the association of curved (quarter/half-barrel) assemblies around a common hydrophobic core through packing interactions that remain plastic and amenable to change.
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
---|
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.
Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
---|
Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
---|
Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, or SPELL.
Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
---|
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
Site | Modification | Modifier | Source | Reference |
---|
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
---|
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.
Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
---|
Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.
Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
---|
Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; download this table as a .txt file using the Download button;
Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
---|
Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; download this table as a .txt file using the Download button;
Evidence ID | Analyze ID | File | Description |
---|