2f1s: Difference between revisions

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[[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2f1s, resolution 1.4Å" />

'''Crystal Structure of a Viral FLIP MC159'''<br />

==Overview==

Death receptor signaling is initiated by the assembly of the, death-inducing signaling complex, which culminates in the activation of, the initiator caspase, either caspase-8 or caspase-10. A family of viral, and cellular proteins, known as FLIP, plays an essential role in the, regulation of death receptor signaling. Viral FLIP (v-FLIP) and short, cellular FLIP (c-FLIPS) inhibit apoptosis by interfering with death, receptor signaling. The structure and mechanisms of v-FLIP and c-FLIPS, remain largely unknown. Here we report a high resolution crystal structure, of MC159, a v-FLIP derived from the molluscum contagiosum virus, which is, a member of the human poxvirus family. Unexpectedly, the two tandem death, effector domains (DEDs) of MC159 rigidly associate with each other through, a hydrophobic interface. Structure-based sequence analysis suggests that, this interface is conserved in the tandem DEDs from other v-FLIP, c-FLIPS, and caspase-8 and -10. Strikingly, the overall packing arrangement between, the two DEDs of MC159 resembles that between the caspase recruitment, domains of Apaf-1 and caspase-9. In addition, each DED of MC159 contains a, highly conserved binding motif on the surface, to which loss-of-function, mutations in MC159 map. These observations, in conjunction with published, evidence, reveal significant insights into the function of v-FLIP and, suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor, signaling.

Death receptor signaling is initiated by the assembly of the death-inducing signaling complex, which culminates in the activation of the initiator caspase, either caspase-8 or caspase-10. A family of viral and cellular proteins, known as FLIP, plays an essential role in the regulation of death receptor signaling. Viral FLIP (v-FLIP) and short cellular FLIP (c-FLIPS) inhibit apoptosis by interfering with death receptor signaling. The structure and mechanisms of v-FLIP and c-FLIPS remain largely unknown. Here we report a high resolution crystal structure of MC159, a v-FLIP derived from the molluscum contagiosum virus, which is a member of the human poxvirus family. Unexpectedly, the two tandem death effector domains (DEDs) of MC159 rigidly associate with each other through a hydrophobic interface. Structure-based sequence analysis suggests that this interface is conserved in the tandem DEDs from other v-FLIP, c-FLIPS, and caspase-8 and -10. Strikingly, the overall packing arrangement between the two DEDs of MC159 resembles that between the caspase recruitment domains of Apaf-1 and caspase-9. In addition, each DED of MC159 contains a highly conserved binding motif on the surface, to which loss-of-function mutations in MC159 map. These observations, in conjunction with published evidence, reveal significant insights into the function of v-FLIP and suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor signaling.

==About this Structure==

2F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2F1S OCA].

2F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F1S OCA].

==Reference==

Line 13:

[[Category: Molluscum contagiosum virus subtype 2]]

[[Category: Single protein]]

[[Category: Jeffrey, P.D.]]

[[Category: Jeffrey, P D.]]

[[Category: Li, F.Y.]]

[[Category: Li, F Y.]]

[[Category: Shi, Y.]]

[[Category: Yu, J.W.]]

[[Category: Yu, J W.]]

[[Category: caspase activation]]

[[Category: death receptor signaling]]

Line 23:

[[Category: flip]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 10:18:~~27 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:48 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2f1s.gif|left|200px]]<br /><applet load="2f1s" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2f1s, resolution 1.4&Aring;" />
 '''Crystal Structure of a Viral FLIP MC159'''<br />
 ==Overview==
-Death receptor signaling is initiated by the assembly of the, death-inducing signaling complex, which culminates in the activation of, the initiator caspase, either caspase-8 or caspase-10. A family of viral, and cellular proteins, known as FLIP, plays an essential role in the, regulation of death receptor signaling. Viral FLIP (v-FLIP) and short, cellular FLIP (c-FLIPS) inhibit apoptosis by interfering with death, receptor signaling. The structure and mechanisms of v-FLIP and c-FLIPS, remain largely unknown. Here we report a high resolution crystal structure, of MC159, a v-FLIP derived from the molluscum contagiosum virus, which is, a member of the human poxvirus family. Unexpectedly, the two tandem death, effector domains (DEDs) of MC159 rigidly associate with each other through, a hydrophobic interface. Structure-based sequence analysis suggests that, this interface is conserved in the tandem DEDs from other v-FLIP, c-FLIPS, and caspase-8 and -10. Strikingly, the overall packing arrangement between, the two DEDs of MC159 resembles that between the caspase recruitment, domains of Apaf-1 and caspase-9. In addition, each DED of MC159 contains a, highly conserved binding motif on the surface, to which loss-of-function, mutations in MC159 map. These observations, in conjunction with published, evidence, reveal significant insights into the function of v-FLIP and, suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor, signaling.
+Death receptor signaling is initiated by the assembly of the death-inducing signaling complex, which culminates in the activation of the initiator caspase, either caspase-8 or caspase-10. A family of viral and cellular proteins, known as FLIP, plays an essential role in the regulation of death receptor signaling. Viral FLIP (v-FLIP) and short cellular FLIP (c-FLIPS) inhibit apoptosis by interfering with death receptor signaling. The structure and mechanisms of v-FLIP and c-FLIPS remain largely unknown. Here we report a high resolution crystal structure of MC159, a v-FLIP derived from the molluscum contagiosum virus, which is a member of the human poxvirus family. Unexpectedly, the two tandem death effector domains (DEDs) of MC159 rigidly associate with each other through a hydrophobic interface. Structure-based sequence analysis suggests that this interface is conserved in the tandem DEDs from other v-FLIP, c-FLIPS, and caspase-8 and -10. Strikingly, the overall packing arrangement between the two DEDs of MC159 resembles that between the caspase recruitment domains of Apaf-1 and caspase-9. In addition, each DED of MC159 contains a highly conserved binding motif on the surface, to which loss-of-function mutations in MC159 map. These observations, in conjunction with published evidence, reveal significant insights into the function of v-FLIP and suggest a mechanism by which v-FLIP and c-FLIPS inhibit death receptor signaling.
 ==About this Structure==
-F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F1S OCA].
+F1S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Molluscum_contagiosum_virus_subtype_2 Molluscum contagiosum virus subtype 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F1S OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Molluscum contagiosum virus subtype 2]]
 [[Category: Single protein]]
-[[Category: Jeffrey, P.D.]]
+[[Category: Jeffrey, P D.]]
-[[Category: Li, F.Y.]]
+[[Category: Li, F Y.]]
 [[Category: Shi, Y.]]
-[[Category: Yu, J.W.]]
+[[Category: Yu, J W.]]
 [[Category: caspase activation]]
 [[Category: death receptor signaling]]
@@ Line 23: / Line 23: @@
 [[Category: flip]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:18:27 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:48 2008''