4kxh

Publication Abstract from PubMed

The deletion of five residues in the loop connecting the N-terminal helix to the core of monomeric human pancreatic ribonuclease leads to the formation of an enzymatically active domain-swapped dimer (desHP). The crystal structure of desHP reveals the generation of an intriguing fibril-like aggregate of desHP molecules that extends along the c crystallographic axis. Dimers are formed by three-dimensional domain swapping. Tetramers are formed by the aggregation of swapped dimers with slightly different quaternary structures. The tetramers interact in such a way as to form an infinite rod-like structure that propagates throughout the crystal. The observed supramolecular assembly captured in the crystal predicts that desHP fibrils could form in solution; this has been confirmed by atomic force microscopy. These results provide new evidence that three-dimensional domain swapping can be a mechanism for the formation of elaborate large assemblies in which the protein, apart from the swapping, retains its original fold.

Three-dimensional domain swapping and supramolecular protein assembly: insights from the X-ray structure of a dimeric swapped variant of human pancreatic RNase.,Pica A, Merlino A, Buell AK, Knowles TP, Pizzo E, D'Alessio G, Sica F, Mazzarella L Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2116-23. doi:, 10.1107/S0907444913020507. Epub 2013 Sep 20. PMID:24100329^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.