Journal:Acta Cryst D:S2059798320010906
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
| - | CYRI-B, also called FAM49B, is a well-conserved eukaryotic protein which interacts with the small GTPase Rac1 to regulate cellular actin assembly <ref name="Shang1">PMID:29632189</ref><ref name="Fort2">PMID:30250061</ref>. Through its interaction with Rac1, CYRI-B controls multiple critical cellular functions including T cell activation <ref name="Shang1">PMID:29632189</ref>, chemotaxis and cell migration <ref name="Fort2">PMID:30250061</ref><ref name="Whitelaw3">PMID:31413787</ref>. CYRI-B has also been described to reduce cellular entry of several bacterial pathogens <ref name="Yuki4">PMID:31285585</ref> and has been suggested to play a role in various cancers <ref name="Long5">PMID:29059164</ref><ref name="Chen6">PMID:31010678</ref>. | + | '''CYRI-B''', also called FAM49B, is a well-conserved eukaryotic protein which '''interacts with the small GTPase Rac1 to regulate cellular actin assembly''' <ref name="Shang1">PMID:29632189</ref><ref name="Fort2">PMID:30250061</ref>. Through its interaction with Rac1, CYRI-B controls multiple critical cellular functions including T cell activation <ref name="Shang1">PMID:29632189</ref>, chemotaxis and cell migration <ref name="Fort2">PMID:30250061</ref><ref name="Whitelaw3">PMID:31413787</ref>. CYRI-B has also been described to reduce cellular entry of several bacterial pathogens <ref name="Yuki4">PMID:31285585</ref> and has been suggested to play a role in various cancers <ref name="Long5">PMID:29059164</ref><ref name="Chen6">PMID:31010678</ref>. |
| - | The structure of CYRI-B has been solved by X-ray crystallography at 2.4 Å resolution. It reveals an entirely α-helical protein | + | The structure of CYRI-B has been solved by X-ray crystallography at 2.4 Å resolution. It reveals an entirely α-helical protein organized into three distinct subdomains. The CYRI-B structure shows significant similarity with a conserved domain of '''CYFIP1''', a '''key component of the WAVE regulatory complex (WRC) that interacts with Rac1 to promote actin polymerisation''' <ref name="Chen7">PMID:21107423</ref>. The study highlights residues crucial for Rac1 binding in both proteins. This suggests that CYRI-B interacts with Rac1 in the same manner as CYFIP1, regulating actin-dependent processes by competition with the WRC for Rac1 binding. The structure provides a better understanding of the many roles played by CYRI-B, and also by other members of the CYRI protein family, in eukaryotic cells. |
| - | <scene name='85/859606/Cv/4'>Crystal structure of CYRI-B</scene>. Cartoon representation of the native CYRI-B from ''Rhincodon typus'' showing the N-terminal (''lime''), Medial (''yellow'') and C-terminal (''royalblue'') subdomains. The myristoylation site of the protein is indicated. This is the first structure of any member of the CYRI family. It reveals a protein comprised solely of α-helices which can be divided into three linear subdomains. The <scene name='85/859606/Cv/5'>N-terminal subdomain</scene> extends until residue 125 and consists of five α-helices, three of which form a 60 Å elongated α-helical hairpin extending the entire length of the protein. <scene name='85/859606/Cv/7'>The Medial subdomain</scene> extends from residues 126 to 214 and exhibits a 90º-broken antiparallel helical hairpin, that covers one face of the N-terminal subdomain. The two antiparallel helices α6 and α9 split at the lowest part to surround the extended α4 helix of the N-terminal subdomain. Finally, the <scene name='85/859606/Cv/8'>C-terminal subdomain</scene> (215-324) consists of six α-helices | + | <scene name='85/859606/Cv/4'>Crystal structure of CYRI-B</scene>. Cartoon representation of the native CYRI-B from ''Rhincodon typus'' showing the N-terminal (''lime''), Medial (''yellow'') and C-terminal (''royalblue'') subdomains. The myristoylation site of the protein is indicated. This is the first structure of any member of the CYRI family. It reveals a protein comprised solely of α-helices which can be divided into three linear subdomains. The <scene name='85/859606/Cv/5'>N-terminal subdomain</scene> extends until residue 125 and consists of five α-helices, three of which form a 60 Å elongated α-helical hairpin extending the entire length of the protein. <scene name='85/859606/Cv/7'>The Medial subdomain</scene> extends from residues 126 to 214 and exhibits a 90º-broken antiparallel helical hairpin, that covers one face of the N-terminal subdomain. The two antiparallel helices α6 and α9 split at the lowest part to surround the extended α4 helix of the N-terminal subdomain. Finally, the <scene name='85/859606/Cv/8'>C-terminal subdomain</scene> (215-324) consists of six α-helices that associate into a globular bundle located at the base of the structure. This bundle caps the lower half of the Medial subdomain and is elevated above helices α1 and α5 of the N-terminal subdomain. In both the native and SeMet structures, the flexible loop composed of residues 171 to 175 was too disordered to build and is therefore missing from the final models. This loop connects helices α7 and α8 of the Medial subdomain. A non-native serine, residual from the purification strategy, is present at the N-terminus of the structure. |
<scene name='85/859606/Cv/9'>CYRI-B and CYFIP1 present a high degree of structural similarity</scene>. CYRI-B showing the N-terminal (''lime''), Medial (''yellow'') and C-terminal (''royalblue'') subdomains. CYFIP1 DUF1394 domain (PDB [[3p8c]]) showing the N-terminal (''green''), Medial (''gold'') and C-terminal (''blue'') subdomains. The presence of an extra hairpin in CYFIP1 is indicated (''darkstateblue''). <scene name='85/859606/Cv/10'>Animation of this scene</scene>. | <scene name='85/859606/Cv/9'>CYRI-B and CYFIP1 present a high degree of structural similarity</scene>. CYRI-B showing the N-terminal (''lime''), Medial (''yellow'') and C-terminal (''royalblue'') subdomains. CYFIP1 DUF1394 domain (PDB [[3p8c]]) showing the N-terminal (''green''), Medial (''gold'') and C-terminal (''blue'') subdomains. The presence of an extra hairpin in CYFIP1 is indicated (''darkstateblue''). <scene name='85/859606/Cv/10'>Animation of this scene</scene>. | ||
Revision as of 10:58, 28 June 2021
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