1s2h: Difference between revisions

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[[Image:1s2h.gif|left|200px]]<br />

[[Image:1s2h.gif|left|200px]]<br /><applet load="1s2h" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1s2h" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1s2h" />

'''The Mad2 spindle checkpoint protein possesses two distinct natively folded states'''<br />

==Overview==

The spindle checkpoint delays chromosome segregation in response to, misaligned sister chromatids during mitosis, thus ensuring the fidelity of, chromosome inheritance. Through binding to Cdc20, the Mad2 spindle, checkpoint protein inhibits the target of this checkpoint, the ubiquitin, protein ligase APC/C(Cdc20). We now show that without cofactor binding or, covalent modification Mad2 adopts two distinct folded conformations at, equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has, been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C, inhibition. Overexpression of a Mad2 mutant that specifically sequesters, N2-Mad2 partially blocks checkpoint signaling in living cells. The two, Mad2 conformers interconvert slowly in vitro, but interconversion is, accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our, results suggest that the unusual two-state behavior of Mad2 is critical, for spindle checkpoint signaling.

The spindle checkpoint delays chromosome segregation in response to misaligned sister chromatids during mitosis, thus ensuring the fidelity of chromosome inheritance. Through binding to Cdc20, the Mad2 spindle checkpoint protein inhibits the target of this checkpoint, the ubiquitin protein ligase APC/C(Cdc20). We now show that without cofactor binding or covalent modification Mad2 adopts two distinct folded conformations at equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C inhibition. Overexpression of a Mad2 mutant that specifically sequesters N2-Mad2 partially blocks checkpoint signaling in living cells. The two Mad2 conformers interconvert slowly in vitro, but interconversion is accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our results suggest that the unusual two-state behavior of Mad2 is critical for spindle checkpoint signaling.

==About this Structure==

1S2H 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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1S2H OCA].

1S2H 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=1S2H OCA].

==Reference==

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[[Category: spindle checkpoint protein]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 19~~:09:~~43 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:12 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1s2h.gif|left|200px]]<br />
+[[Image:1s2h.gif|left|200px]]<br /><applet load="1s2h" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1s2h" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1s2h" />
 '''The Mad2 spindle checkpoint protein possesses two distinct natively folded states'''<br />
 ==Overview==
-The spindle checkpoint delays chromosome segregation in response to, misaligned sister chromatids during mitosis, thus ensuring the fidelity of, chromosome inheritance. Through binding to Cdc20, the Mad2 spindle, checkpoint protein inhibits the target of this checkpoint, the ubiquitin, protein ligase APC/C(Cdc20). We now show that without cofactor binding or, covalent modification Mad2 adopts two distinct folded conformations at, equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has, been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C, inhibition. Overexpression of a Mad2 mutant that specifically sequesters, N2-Mad2 partially blocks checkpoint signaling in living cells. The two, Mad2 conformers interconvert slowly in vitro, but interconversion is, accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our, results suggest that the unusual two-state behavior of Mad2 is critical, for spindle checkpoint signaling.
+The spindle checkpoint delays chromosome segregation in response to misaligned sister chromatids during mitosis, thus ensuring the fidelity of chromosome inheritance. Through binding to Cdc20, the Mad2 spindle checkpoint protein inhibits the target of this checkpoint, the ubiquitin protein ligase APC/C(Cdc20). We now show that without cofactor binding or covalent modification Mad2 adopts two distinct folded conformations at equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C inhibition. Overexpression of a Mad2 mutant that specifically sequesters N2-Mad2 partially blocks checkpoint signaling in living cells. The two Mad2 conformers interconvert slowly in vitro, but interconversion is accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our results suggest that the unusual two-state behavior of Mad2 is critical for spindle checkpoint signaling.
 ==About this Structure==
-S2H 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S2H OCA].
+S2H 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=1S2H OCA].
 ==Reference==
@@ Line 24: / Line 23: @@
 [[Category: spindle checkpoint protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:09:43 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:57:12 2008''