1gjz: Difference between revisions
From Proteopedia
Jump to navigationJump to search
New page: left|200px<br /> <applet load="1gjz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1gjz" /> '''SOLUTION STRUCTURE OF A DIMERIC N-TERMINAL ... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1gjz. | [[Image:1gjz.jpg|left|200px]]<br /><applet load="1gjz" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1gjz" size=" | |||
caption="1gjz" /> | caption="1gjz" /> | ||
'''SOLUTION STRUCTURE OF A DIMERIC N-TERMINAL FRAGMENT OF HUMAN UBIQUITIN'''<br /> | '''SOLUTION STRUCTURE OF A DIMERIC N-TERMINAL FRAGMENT OF HUMAN UBIQUITIN'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
Previous peptide dissection and kinetic experiments have indicated that in, vitro folding of ubiquitin may proceed via transient species in which, native-like structure has been acquired in the first 45 residues. A, peptide fragment, UQ(1-51), encompassing residues 1 to 51 of ubiquitin was, produced in order to test whether this portion has propensity for, independent self-assembly. Surprisingly, the construct formed a folded, symmetrical dimer that was stabilised by 0.8 M sodium sulphate at 298 K, (the S state). The solution structure of the UQ(1-51) dimer was determined, by multinuclear NMR spectroscopy. Each subunit of UQ(1-51) consists of an, N-terminal beta-hairpin followed by an alpha-helix and a final, beta-strand, with orientations similar to intact ubiquitin. The dimer is, formed by the third beta-strand of one subunit interleaving between the, hairpin and third strand of the other to give a six-stranded beta-sheet, with the two alpha-helices sitting on top. The helix-helix and strand, portions of the dimer interface also mimic related features in the, structure of ubiquitin. The structural specificity of the UQ(1-51) peptide, is tuneable: as the concentration of sodium sulphate is decreased, near-native alternative conformations are populated in slow chemical, exchange. Magnetization transfer experiments were performed to, characterize the various species present in 0.35 M sodium sulphate, namely, the S state and two minor forms. Chemical shift differences suggest that, one minor form is very similar to the S state, while the other experiences, a significant conformational change in the third strand. A segmental, rearrangement of the third strand in one subunit of the S state would, render the dimer asymmetric, accounting for most of our results. Similar, small-scale transitions in proteins are often invoked to explain solvent, exchange at backbone amide proton sites that have an intermediate level of, protection. | Previous peptide dissection and kinetic experiments have indicated that in, vitro folding of ubiquitin may proceed via transient species in which, native-like structure has been acquired in the first 45 residues. A, peptide fragment, UQ(1-51), encompassing residues 1 to 51 of ubiquitin was, produced in order to test whether this portion has propensity for, independent self-assembly. Surprisingly, the construct formed a folded, symmetrical dimer that was stabilised by 0.8 M sodium sulphate at 298 K, (the S state). The solution structure of the UQ(1-51) dimer was determined, by multinuclear NMR spectroscopy. Each subunit of UQ(1-51) consists of an, N-terminal beta-hairpin followed by an alpha-helix and a final, beta-strand, with orientations similar to intact ubiquitin. The dimer is, formed by the third beta-strand of one subunit interleaving between the, hairpin and third strand of the other to give a six-stranded beta-sheet, with the two alpha-helices sitting on top. The helix-helix and strand, portions of the dimer interface also mimic related features in the, structure of ubiquitin. The structural specificity of the UQ(1-51) peptide, is tuneable: as the concentration of sodium sulphate is decreased, near-native alternative conformations are populated in slow chemical, exchange. Magnetization transfer experiments were performed to, characterize the various species present in 0.35 M sodium sulphate, namely, the S state and two minor forms. Chemical shift differences suggest that, one minor form is very similar to the S state, while the other experiences, a significant conformational change in the third strand. A segmental, rearrangement of the third strand in one subunit of the S state would, render the dimer asymmetric, accounting for most of our results. Similar, small-scale transitions in proteins are often invoked to explain solvent, exchange at backbone amide proton sites that have an intermediate level of, protection. | ||
==Disease== | |||
Known disease associated with this structure: Cleft palate, isolated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191339 191339]] | |||
==About this Structure== | ==About this Structure== | ||
1GJZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 1GJZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GJZ OCA]. | ||
==Reference== | ==Reference== | ||
| Line 22: | Line 24: | ||
[[Category: ubiquitin]] | [[Category: ubiquitin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:54:13 2008'' | ||
