Sandbox Reserved 334: Difference between revisions
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=Ribonuclease S= | |||
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{{STRUCTURE_1d5h | PDB=1d5h | SCENE= }} | |||
Ribonuclease S (RNase S) is a modified version of Ribonuclease A, a pancreatic nuclease found in vertebrates <ref name= “redux”> PMID:21079871</ref>. RNase S is synthesized by the proteolytic cleavage of RNase A by subtilisin <ref name= “Original”> PMID:11015216</ref>. Neither of the resulting fragments have ribonuclease activity, but together as the RNase S complex it has full enzymatic activity <ref name= “def”> PMID:8453373</ref>. As a ribonuclease, RNase S functions to catalyze the hydrolysis of certain internucleotide linkages of RNA <ref name = “def” />. | |||
=Structure and Function= | |||
RNase S is composed of two fragments: the small fragment, <scene name='Sandbox_Reserved_334/S-peptide/1'>S-peptide</scene> (residues 1-20), and the large fragment, <scene name='Sandbox_Reserved_334/S-protein/1'>S-protein</scene> (residues 21-124)<ref name = “Original” />. These fragments remain tightly bound by non-covalent interactions<ref name= “abc”> PMID:16415350</ref>. The only observed change in covalent structure during the conversion of RNase A to RNase S is the hydrolysis of the peptide bond between the residues 20 and 21 <ref name = “redux” />. This complex (RNase S) conserves the catalytic activity and native conformation of uncleaved RNase A, but shows a reduced conformational stability <ref name = "abc"/>. Two hydrophobic residues, methionine 13 and phenylalanine 8, of the S-peptide contribute significantly to the stability of RNase S,<ref name = “Original” /> while three residues (Phe 8, His 12, and Met 13) seem to be essential for the for the formation of the catalytically active RNase S<ref name = “def” />. It has four disulfide bonds that impose rigidity to the protein <ref name = "abc"/>. RNase S can form either as a monomer or dimer, which have similar backbone structures except for in the hinge loop region <ref name = "abc"/>. The dimer has a ''trans'' Asn113-Pro114 peptide bond in the hinge loop, whereas the monomer has a ''cis'' bond in this position <ref name = "abc"/>. The RNase S dimer shows significant activity against poly(A)poly(U) sequences and single stranded RNA, similar to the enzymatic activity of RNase A <ref name = "abc"/>. | |||
=Mechanism= | |||
==Dimer Formation== | |||
Proteolysis of RNase S can activate oligomerization by destabilizing the native state <ref name = "abc"/>. This occurs via the three dimensional domain-swapping mechanism <ref name = "abc"/>. In this mechanism two monomers trade structural motifs called swap domains which adopt essentially identical conformations in the monomeric and oligomeric forms <ref name = "abc"/>. RNase S oligomerizes by swapping C termini, which are not cut by subtilisin <ref name = "abc"/>. | |||
==Dissociation of RNase S Dimers== | |||
There are two possible pathways through which RNase S dimers dissociate; however, it is believed that dissociation occurs mainly through pathway 1 <ref name = "abc"/>. Pathway 1 involves the rapid separation and dissociation of the dimers due to a weakened union between the swapped β-strand and the S-protein moiety caused by the separation of S-peptide from one subunit which is the rate limiting step <ref name = "abc"/>. Whereas, pathway 2 has a rate limiting step of the separation of a swapped β-strand and hinge loop and the accompanying loss of stabilizing interactions <ref name = "abc"/>. | |||
=References= | |||
<references /> | |||