Structural and Motional Changes Induced in apo-S100A1 Protein by the Disulfide Formation between Its Cys 85 Residue and <img src="http://pubs.acs.org/images/gifchars/beta2.gif" border="0" align
详细信息 查看全文
- 作者：Igor Zhukov ; Andrzej Ejchart ; Andrzej Bierzy<img src="http ; //pubs.acs.org/images/entities/nacute.gif" border="0">ski
- 刊名：Biochemistry
- 出版年：2008
- 出版时间：January 15, 2008
- 年：2008
- 卷：47
- 期：2
- 页码：640 - 650
- 全文大小：511K
- 年卷期：v.47,no.2(January 15, 2008)
- ISSN：1520-4995
文摘
Recently, we have shown (Goch, G., Vdovenko, S., Koz<IMG SRC="/images/entities/lstrok.gif">owska, H., and Bierzy
ski, A. (2005)FEBS J. 272, 2557-2565) that the chemical modification of Cys 85 residue of S100A1 protein bydisulfide bond formation with small thiols such as glutathione, cysteine, or 
-mercaptoethanol (ME)leads to a dramatic increase of the protein affinity for calcium. Therefore, the biological function ofS100A1 as a calcium signal transmitter is probably regulated by the redox potential within the cell.Systematic, structural studies of various mixed disulfides of S100A1 in the apo and holo states are necessaryto elucidate the mechanism of this phenomenon. Using NMR methods we have determined the structureof apo-S100A1-ME and, on the basis of 15N nuclear magnetic relaxation data, we have characterizedthe structural dynamics of both: modified and unmodified molecules of apo-S100A1. The followingeffects of ME modification have been observed: (1) Helices IV and IV' of two protein subunits areelongated by five residues (85-89). (2) Conformation of the calcium binding N-terminal loops isdramatically changed, and structural flexibility of the N-loops as well as C-loops markedly increases. (3)The angle between helices I and IV increases by ~20
and between helices IV and IV' decreases by~35. All these observations lead to the conclusion that ME modification of apo-S100A1 makes itsstructure more similar to that of holo-S100A1, so that it becomes much better adjusted for calciumcoordination.
ski, A. (2005)FEBS J. 272, 2557-2565) that the chemical modification of Cys 85 residue of S100A1 protein bydisulfide bond formation with small thiols such as glutathione, cysteine, or -mercaptoethanol (ME)leads to a dramatic increase of the protein affinity for calcium. Therefore, the biological function ofS100A1 as a calcium signal transmitter is probably regulated by the redox potential within the cell.Systematic, structural studies of various mixed disulfides of S100A1 in the apo and holo states are necessaryto elucidate the mechanism of this phenomenon. Using NMR methods we have determined the structureof apo-S100A1-ME and, on the basis of 15N nuclear magnetic relaxation data, we have characterizedthe structural dynamics of both: modified and unmodified molecules of apo-S100A1. The followingeffects of ME modification have been observed: (1) Helices IV and IV' of two protein subunits areelongated by five residues (85-89). (2) Conformation of the calcium binding N-terminal loops isdramatically changed, and structural flexibility of the N-loops as well as C-loops markedly increases. (3)The angle between helices I and IV increases by ~20 and between helices IV and IV' decreases by~35. All these observations lead to the conclusion that ME modification of apo-S100A1 makes itsstructure more similar to that of holo-S100A1, so that it becomes much better adjusted for calciumcoordination.