Journal:MicroPubl Biol:000669
From Proteopedia
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Based on our analyses, the uncharacterized ''Gossypium hirsutum'' protein (UniProt A0A1U8N485; NCBI XP_016732659) here referred to as GhVAB-A0A1U8N485, identified as a gene of unknown function in cotton species (Chen ''et al''., 2020<ref name='Chen'>PMID: 32313247</ref>), contains two domains: a VAN3-binding protein-like, auxin canalisation domain (domain of unknown function, DUF828) and a pleckstrin homology (PH) domain. The specific function of these domains is unknown but they are often found together in proteins of the VAN3-binding (VAB) protein family, also known as the FORKED-like (FL) family. It is proposed that members of this plant-specific family in Arabidopsis are involved in aiding asymmetrical localization of PIN1 (PINFORMED) an auxin transport protein responsible for establishing vein patterns and numbers in leaves (Hou ''et al''., 2010<ref name='Hou'>PMID: 20626652</ref>). GhVAB-A0A1U8N485 is most similar in sequence to the Group 3 FL proteins in Arabidopsis, FL5-7, which appear to be localized to the Golgi apparatus and decrease leaf size when mutated. | Based on our analyses, the uncharacterized ''Gossypium hirsutum'' protein (UniProt A0A1U8N485; NCBI XP_016732659) here referred to as GhVAB-A0A1U8N485, identified as a gene of unknown function in cotton species (Chen ''et al''., 2020<ref name='Chen'>PMID: 32313247</ref>), contains two domains: a VAN3-binding protein-like, auxin canalisation domain (domain of unknown function, DUF828) and a pleckstrin homology (PH) domain. The specific function of these domains is unknown but they are often found together in proteins of the VAN3-binding (VAB) protein family, also known as the FORKED-like (FL) family. It is proposed that members of this plant-specific family in Arabidopsis are involved in aiding asymmetrical localization of PIN1 (PINFORMED) an auxin transport protein responsible for establishing vein patterns and numbers in leaves (Hou ''et al''., 2010<ref name='Hou'>PMID: 20626652</ref>). GhVAB-A0A1U8N485 is most similar in sequence to the Group 3 FL proteins in Arabidopsis, FL5-7, which appear to be localized to the Golgi apparatus and decrease leaf size when mutated. | ||
| - | The AlphaFold structure model for GhVAB-A0A1U8N485 predicted two distinct folding regions with high confidence from Gly111-Arg224 and Gln259-Val366. The first region, from residues 111-224, consists primarily of four alpha helices and contains most of the DUF828 domain. The second region contains the PH domain residues 259-366 and consists of a single alpha helix and seven anti-parallel beta sheets. Although VAB proteins are only found in plants, the PH domain structure is found in proteins across kingdoms of life. PH domains often localize to membranes, contain a conserved set of secondary structures and commonly bind phosphatidylinositol phosphates involved in signaling pathways (Le Huray ''et al''., 2022<ref name='Huray'>PMID: 35857458</ref>). From published structures of other PH domains (''Saccharomyces cerevisiae'' Avo1, PDB [[3ulb]] and human protein kinase B/Akt, PDB [[1h10]]), the core of the PH domain is shown to be a seven-stranded anti-parallel beta-sandwich closed at its C-terminus by an alpha-helix. At the N-terminus of this beta-sandwich are three variable loops containing positively charged residues forming a pocket of basic residues that bind negatively-charged phosphoinositides. | + | The AlphaFold structure model for GhVAB-A0A1U8N485 predicted <scene name='94/945522/Cv/3'>two distinct folding regions with high confidence from Gly111-Arg224 and Gln259-Val366</scene>. The first region (colored in blue), from residues 111-224, consists primarily of four alpha helices and contains most of the DUF828 domain. The second region (in green) contains the PH domain residues 259-366 and consists of a single alpha helix and seven anti-parallel beta sheets. Although VAB proteins are only found in plants, the PH domain structure is found in proteins across kingdoms of life. PH domains often localize to membranes, contain a conserved set of secondary structures and commonly bind phosphatidylinositol phosphates involved in signaling pathways (Le Huray ''et al''., 2022<ref name='Huray'>PMID: 35857458</ref>). From published structures of other PH domains (''Saccharomyces cerevisiae'' Avo1, PDB [[3ulb]] and human protein kinase B/Akt, PDB [[1h10]]), the core of the PH domain is shown to be a seven-stranded anti-parallel beta-sandwich closed at its C-terminus by an alpha-helix. At the N-terminus of this beta-sandwich are three variable loops containing positively charged residues forming a pocket of basic residues that bind negatively-charged phosphoinositides. |
When the PH domain of human protein kinase B/Akt containing a bound phosphatidylinositol trisphosphate ligand (PDB [[1h10]]) was overlaid with the GhVAB-A0A1U8N485 PH domain, a deep binding pocket accommodating the phosphoinositide ligand was observed in the structure. Indeed, this GhVAB-A0A1U8N485 binding pocket is lined with positively-charged amino acids that could interact with the negatively-charge phosphate groups and residues within this pocket are highly-conserved based on ConSurf analysis. A structure-based alignment between GhVAB-A0A1U8N485 and human protein kinase B/Akt indicated that two of the five ligand-binding residues in B/Akt are completely conserved in GhVAB-A0A1U8N485, with two others being conservative substitutions (Thomas ''et al''., 2002<ref name='Thomas'>PMID: 12176338</ref>). Evidence from sequence and structure features support that GhVAB-A0A1U8N485 is part of the VAN3-binding protein family. Furthermore, based on functional reports of other VAN3-binding proteins as well as structural analysis of our protein, GhVAB-A0A1U8N485 might be involved in regulating leaf size or vein development in cotton plants by binding phosphoinositides as part of an auxin signaling pathway. | When the PH domain of human protein kinase B/Akt containing a bound phosphatidylinositol trisphosphate ligand (PDB [[1h10]]) was overlaid with the GhVAB-A0A1U8N485 PH domain, a deep binding pocket accommodating the phosphoinositide ligand was observed in the structure. Indeed, this GhVAB-A0A1U8N485 binding pocket is lined with positively-charged amino acids that could interact with the negatively-charge phosphate groups and residues within this pocket are highly-conserved based on ConSurf analysis. A structure-based alignment between GhVAB-A0A1U8N485 and human protein kinase B/Akt indicated that two of the five ligand-binding residues in B/Akt are completely conserved in GhVAB-A0A1U8N485, with two others being conservative substitutions (Thomas ''et al''., 2002<ref name='Thomas'>PMID: 12176338</ref>). Evidence from sequence and structure features support that GhVAB-A0A1U8N485 is part of the VAN3-binding protein family. Furthermore, based on functional reports of other VAN3-binding proteins as well as structural analysis of our protein, GhVAB-A0A1U8N485 might be involved in regulating leaf size or vein development in cotton plants by binding phosphoinositides as part of an auxin signaling pathway. | ||
| - | + | <b>References</b><br> | |
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| - | <b>References</b><br> | + | |
<references/> | <references/> | ||
</StructureSection> | </StructureSection> | ||
__NOEDITSECTION__ | __NOEDITSECTION__ | ||
Revision as of 14:01, 9 January 2023
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
