Human CC Chemokine I-309, Structural Consequences of the Additional Disulfide Bond
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- 作者：David W. Keizer ; Matthew P. Crump ; Tae Woo Lee ; Carolyn M. Slupsky ; Ian Clark-Lewis ; and Brian D. Sykes
- 刊名：Biochemistry
- 出版年：2000
- 出版时间：May 23, 2000
- 年：2000
- 卷：39
- 期：20
- 页码：6053 - 6059
- 全文大小：172K
- 年卷期：v.39,no.20(May 23, 2000)
- ISSN：1520-4995
文摘
I-309 is a member of the CC subclass of chemokines and is one of only three human chemokinesknown to contain an additional, third disulfide bond. The three-dimensional solution structure of I-309was determined by 1H nuclear magnetic resonance spectroscopy and dynamic simulated annealing. Thestructure of I-309, which remains monomeric at high concentrations, was determined on the basis of 978experimental restraints. The N-terminal region of I-309 was disordered, as has been previously observedfor the CC chemokine eotaxin but not others such as MCP-1 and RANTES. This was followed in I-309by a well-ordered region between residues 13 and 69 that consisted of a 310-helix, a triple-strandedantiparallel 
fchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet, and finally a C-terminal fchars/alpha.gif" BORDER=0>-helix. Root-mean-square deviations of 0.61 and 1.16 wereobserved for the backbone and heavy atoms, respectively. A comparison of I-309 to eotaxin and HCC-2revealed a significant structural change in the C-terminal region of the protein. The fchars/alpha.gif" BORDER=0>-helix normallypresent in chemokines was terminated early and was followed by a short section of extended strand.These changes were a direct result of the additional disulfide bond present in this protein. An examinationof the I-309 structure will aid in an understanding of the specificity of this protein with its receptor,CCR8.
fchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet, and finally a C-terminal fchars/alpha.gif" BORDER=0>-helix. Root-mean-square deviations of 0.61 and 1.16 wereobserved for the backbone and heavy atoms, respectively. A comparison of I-309 to eotaxin and HCC-2revealed a significant structural change in the C-terminal region of the protein. The fchars/alpha.gif" BORDER=0>-helix normallypresent in chemokines was terminated early and was followed by a short section of extended strand.These changes were a direct result of the additional disulfide bond present in this protein. An examinationof the I-309 structure will aid in an understanding of the specificity of this protein with its receptor,CCR8.