3cae | pdb_00003cae
Structure of NNQQNY as an insert in T7 endonuclease I
Structural highlights
FunctionENDO_BPT7 Junction-resolving enzyme that selectively binds and cleaves four-way (Holliday) DNA junctions present after viral genomic replication. These intermediates are created during DNA repair, processing of stalled replication forks and homologous genetic recombination. Introduces two nicks on the two non-crossing strands, at 5' sides of the junction. Participates also together with gp6 in the degradation of host chromosome to provide nucleotides for phage DNA synthesis.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNumerous human disorders are associated with the formation of protein fibrils. The fibril-forming capacity of a protein has been found in recent studies to be determined by a short segment of residues that forms a dual beta-sheet, called a steric zipper, in the spine of the fibril. The question arises as to whether a fibril-forming segment, when inserted within the sequence of a globular protein, will invariably cause the protein to form fibrils. Here we investigate this question by inserting the known fibril-forming segment NNQQNY into the globular enzyme, T7 endonuclease I. From earlier studies, we know that in its fibril form, NNQQNY is in an extended conformation. We first found that the inserted NNQQNY stimulates fibril formation of T7 endonuclease I in solution. Thus NNQQNY within T7 endonuclease I can exist in an extended conformation, capable of forming the steric zipper in the core of a fibril. We also found that T7 endonuclease I folds into a decamer that does not form fibrils. We determined the structure of the decamer by X-ray crystallography, finding an unusual oligomer without point group symmetry, and finding that the NNQQNY segments within the decamer adopt two twisted conformations, neither is apparently able to fibrillize. We conclude that twisting of fibril forming sequences from the fully extended conformation, imposed by the context of their placement in proteins, can interfere with fibril formation. The structure of a fibril-forming sequence, NNQQNY, in the context of a globular fold.,Guo Z, Eisenberg D Protein Sci. 2008 Sep;17(9):1617-23. Epub 2008 Jun 13. PMID:18552127[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
