Sandbox Reserved 1106: Difference between revisions
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<scene name='82/829359/Domains_ago1/2'>Domains</scene> | <scene name='82/829359/Domains_ago1/2'>Domains</scene> | ||
For more details on the 3D structure domains, see the page [[Argonaute 3D structures]] in the rubric Argonaute 1 | |||
==== Primary Structure ==== | ==== Primary Structure ==== | ||
The Ago1 protein has the same 4 primary domains as all | The Ago1 protein has the same 4 primary domains as all argonaute proteins (N, PAZ, Mid, PIWI, described in the page [[Argonaute]]) and the two linker regions L1 (also called DUF1785 domain) and L2. In fact, there are 84% of similitudes between the primary sequence of hAgo1 and that of hAgo2. The main structural difference between the two similar proteins is that the N domain of AGO1 interacts with the L1, L2 and PIWI domains via residues 18-48 and 138-173. | ||
Besides, Argonaute 1 can be found in a lot of phylogenetic groups, with different structure. For example, in the plant ''Brachypodium distachyon'', where 10 argonautes proteins have been discovered, BdAGO1 lacks the N and Mid domains. This particularity explains the small size of this protein with only 624 residues. Moreover, BdAGO1 is related to Ago1 | Besides, Argonaute 1 can be found in a lot of phylogenetic groups, with different structure. For example, in the plant ''Brachypodium distachyon'', where 10 argonautes proteins have been discovered, BdAGO1 lacks the N and Mid domains. This particularity explains the small size of this protein with only 624 residues. Moreover, BdAGO1 is functionally related to Ago1 as both proteins lack endonuclease activity. Indeed, the catalytic tetrad of its PIWI domain is disabled through the absence of the last D/H residue in the domain. | ||
However, the AtAGO1 (from ''Arabidopsis thaliana''), which can be | However, the AtAGO1 (from ''Arabidopsis thaliana''), which can be found in the nucleus and the cytoplasm of the plant, includes a Mid domain and has an homologous conformation to BdAO9, BdAGO11, BdAGO12, BdAGO15, and BdAGO16. On the other hand, BdAGO1 has AtAGO4 as its closest homolog (like BaAGO2, BdAGO3 and BdAGO4), even if the AtAGO4 possess a Mid Domain. | ||
==== | ==== Proteins Associating with Ago1 ==== | ||
The Argonaute 1 protein can be associated with others molecular components of the cell. | The Argonaute 1 protein can be associated with others molecular components of the cell. In fact, proteomic analysis has demonstrated that RNase III Dicer binds hAgo1 through the PIWI domain (see page on argonaute) and also, at least, four other proteins in specific association with hAgo1: | ||
• TNRC6B isoform 1 / KIAA1093 (175kDa) which has RRM motif at C-term to recognize RNA, and also GW repeats (trinucleotide motifs) | • TNRC6B isoform 1 / KIAA1093 (175kDa) which has RRM motif at C-term to recognize RNA, and also GW repeats (trinucleotide motifs) | ||
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• PRMT5 (arginine methyl-transferase) (70kDa) | • PRMT5 (arginine methyl-transferase) (70kDa) | ||
• | • Additionally, the translation factor eEF1α (50kDa) is thought to associate with AGO1 | ||
==== hAgo1 in a complex with let-7 ==== | ==== hAgo1 in a complex with let-7 ==== | ||
The hAgo1 interact with an endogenous let-7 in a | The hAgo1 interact with an endogenous let-7 in a similar manner to the manner in which hAgo2 interact with miR20a, but with some slight differences. | ||
From a domain point of view, the position of L1 linker is the same for hAgo1/let-7 and hAgo2/miR20a, | From a domain point of view, the position of L1 linker is the same for hAgo1/let-7 and hAgo2/miR20a. Also, the N subdomain (from residues K49 to S137 of the N domain) interacts with the endogenous sequence in a loosely similar way for both hAgo1 and hAgo2 except a 3A translation toward the PIWI domain in hAgo1. Besides the piece of information gets from the N subdomain may suggest an interaction with the guide-target duplexes. On the other hand, the PAZ domain is folded differently in hAgo1/let-7 in order to be placed away from the PIWI domain. | ||
Then, from a nucleotide point of view, hAgo1 shows 6 RNA-specific interactions with ribose 2’OH of let-7 (U1, G2, G4, G5, A7 and A8). There are either direct or water-mediated through the side- or main- chain atoms of hAgo1 like for hAgo2/miR20a. However, there is one interaction presents in hAgo2/miR20a that is missing in hAgo1/let-7 ; it is the one with U6 since this base is slightly modified because of the shift of α7 in the L2 toward the N domain. Furthermore, the first adenine base has a syn conformation around the glycosidic bond and the last two bases are piled in the PAZ domain | Then, from a nucleotide point of view, hAgo1 shows 6 RNA-specific interactions with ribose 2’OH of let-7 (U1, G2, G4, G5, A7 and A8). There are either direct or water-mediated through the side- or main- chain atoms of hAgo1 like for hAgo2/miR20a. However, there is one interaction presents in hAgo2/miR20a that is missing in hAgo1/let-7 ; it is the one with U6 since this base is slightly modified because of the shift of α7 in the L2 toward the N domain. Furthermore, the first adenine base has a syn conformation around the glycosidic bond and the last two bases are piled in the PAZ domain | ||
