1h8x
From Proteopedia
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DOMAIN-SWAPPED DIMER OF A HUMAN PANCREATIC RIBONUCLEASE VARIANT
Overview
BACKGROUND: Domain swapping has been proposed as a mechanism that explains, the evolution from monomeric to oligomeric proteins. Bovine and human, pancreatic ribonucleases are monomers with no biological properties other, than their RNA cleavage ability. In contrast, the closely related bovine, seminal ribonuclease is a natural domain-swapped dimer that has special, biological properties, such as cytotoxicity to tumour cells. Several, recombinant ribonuclease variants are domain-swapped dimers, but a, structure of this kind has not yet been reported for the human enzyme., RESULTS: The crystal structure at 2 A resolution of an engineered, ribonuclease variant called PM8 reveals a new kind of domain-swapped, dimer, based on the change of N-terminal domains between the two subunits., The swapping is fastened at both hinge peptides by the newly introduced, Gln101, involved in two intermolecular hydrogen bonds and in a stacking, interaction between residues of different chains. Two antiparallel salt, bridges and water-mediated hydrogen bonds complete a new interface between, subunits, while the hinge loop becomes organized in a 3(10) helix, structure. CONCLUSIONS: Proteins capable of domain swapping may quickly, evolve toward an oligomeric form. As shown in the present structure, a, single residue substitution reinforces the quaternary structure by forming, an open interface. An evolutionary advantage derived from the new, oligomeric state will fix the mutation and favour others, leading to a, more extended complementary dimerization surface, until domain swapping is, no longer necessary for dimer formation. The newly engineered swapped, dimer reported here follows this hypothetical pathway for the rapid, evolution of proteins.
About this Structure
1H8X is a Single protein structure of sequence from Homo sapiens. Active as Pancreatic ribonuclease, with EC number 3.1.27.5 Full crystallographic information is available from OCA.
Reference
The structure of an engineered domain-swapped ribonuclease dimer and its implications for the evolution of proteins toward oligomerization., Canals A, Pous J, Guasch A, Benito A, Ribo M, Vilanova M, Coll M, Structure. 2001 Oct;9(10):967-76. PMID:11591351
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