SARM1: Difference between revisions

Line 11:

== Structural highlights ==

The 3D structure of SARM1 shows the <scene name='91/918463/Cv/2'>octamer structure</scene> with outer ring dimension of 200A, inner ring of 45A and thickness of 60A<ref>PMID:33053563</ref>. The 3 domains of SARM1 are <scene name='91/918463/Cv/3'>ARM, SAM and TIR</scene>. The <scene name='91/918463/Cv/4'>interaction of the ARM and TIR domains cause</scene> the autoinhibition of SARM1. <scene name='91/918463/Cv1/1'>NAD(+) binding pocket is at the concave side</scene> of the ARM domain. <scene name='91/918463/Cv1/3'>NAD(+)/protein interactions</scene>.

The 3D structure of SARM1 shows the <scene name='91/918463/Cv/2'>octamer structure</scene> with outer ring dimension of 200A, inner ring of 45A and thickness of 60A<ref>PMID:33053563</ref>. The 3 domains of SARM1 are <scene name='91/918463/Cv/3'>ARM, SAM and TIR</scene>. The <scene name='91/918463/Cv/4'>interaction of the ARM and TIR domains cause</scene> the autoinhibition of SARM1. <scene name='91/918463/Cv1/1'>NAD(+) binding pocket is at the concave side</scene> of the ARM domain. <scene name='91/918463/Cv1/3'>NAD(+)/protein interactions</scene>. The domain topology includes an N-terminal ARM domain, followed by two SAM and one TIR domain. NADase activity requires homo-oligomerization of TIR domains<ref>PMID:35334231</ref>, which is naturally facilitated by the SAM domains through complementing electrostatic and hydrophobic interactions that assembles eight protomers into a closed ring structure<ref>PMID:31278906</ref>,<ref>PMID:31439792</ref>. The ARM domain inhibits NADase activity in cultured cells and in axons<ref>PMID:27671644</ref>. In the auto-inhibitory conformation, a tightly packed arrangement of overlapping ARM domains surrounds the SAM core ring and supports TIR docking in a way that keeps them separated from each other to prevent their oligomerization and NADase activity. Accordingly, SARM1 activation involves a conformational re-arrangement that would allow nearing of the TIR domains, as demonstrated by the introduction of NMN or by gain-of-function point mutations that disturb ARM-TIR interactions<ref>PMID:33185189</ref>,<ref>PMID:32755591</ref>,<ref>PMID:33468661</ref>,<ref>PMID:33053563</ref>.

==3D structures of SARM1==

[[SARM1 3D structures]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 11: / Line 11: @@
 == Structural highlights ==
-The 3D structure of SARM1 shows the <scene name='91/918463/Cv/2'>octamer structure</scene> with outer ring dimension of 200A, inner ring of 45A and thickness of 60A<ref>PMID:33053563</ref>. The 3 domains of SARM1 are <scene name='91/918463/Cv/3'>ARM, SAM and TIR</scene>. The <scene name='91/918463/Cv/4'>interaction of the ARM and TIR domains cause</scene> the autoinhibition of SARM1. <scene name='91/918463/Cv1/1'>NAD(+) binding pocket is at the concave side</scene> of the ARM domain. <scene name='91/918463/Cv1/3'>NAD(+)/protein interactions</scene>.
+The 3D structure of SARM1 shows the <scene name='91/918463/Cv/2'>octamer structure</scene> with outer ring dimension of 200A, inner ring of 45A and thickness of 60A<ref>PMID:33053563</ref>. The 3 domains of SARM1 are <scene name='91/918463/Cv/3'>ARM, SAM and TIR</scene>. The <scene name='91/918463/Cv/4'>interaction of the ARM and TIR domains cause</scene> the autoinhibition of SARM1. <scene name='91/918463/Cv1/1'>NAD(+) binding pocket is at the concave side</scene> of the ARM domain. <scene name='91/918463/Cv1/3'>NAD(+)/protein interactions</scene>.  The domain topology includes an N-terminal ARM domain, followed by two SAM and one TIR domain. NADase activity requires homo-oligomerization of TIR domains<ref>PMID:35334231</ref>, which is naturally facilitated by the SAM domains through complementing electrostatic and hydrophobic interactions that assembles eight protomers into a closed ring structure<ref>PMID:31278906</ref>,<ref>PMID:31439792</ref>. The ARM domain inhibits NADase activity in cultured cells and in axons<ref>PMID:27671644</ref>. In the auto-inhibitory conformation, a tightly packed arrangement of overlapping ARM domains surrounds the SAM core ring and supports TIR docking in a way that keeps them separated from each other to prevent their oligomerization and NADase activity. Accordingly, SARM1 activation involves a conformational re-arrangement that would allow nearing of the TIR domains, as demonstrated by the introduction of NMN or by gain-of-function point mutations that disturb ARM-TIR interactions<ref>PMID:33185189</ref>,<ref>PMID:32755591</ref>,<ref>PMID:33468661</ref>,<ref>PMID:33053563</ref>.
 ==3D structures of SARM1==
 [[SARM1 3D structures]]