Sandbox 1: Difference between revisions

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The distal face binds to diverse A-rich sequences in mRNAs and SRNAs. Studies have demonstrade that an A-rich motif is critical for Hfq-mediated regulation.

Rim binds to UA-rich sequences. This kind of bind improve the interaction of the HFQ with the RNAs

==RNA binding sites==

The ring-like architecture of the Hfq exposes two well characterized RNA binding sites referred to as “proximal”, representing the surface on which the amino (N)-terminal α-helix is exposed, and “distal” face, corresponding to the opposite surface of the proximal (Vogel & Luisi, 2011; Updegrove et al., 2016). In addition, recently studies have shown the presence of other two binding sites referred to as “lateral” or “rim” face, corresponding to the outer ring of the ring-like structure, and the carboxy (C)-terminal tail (Faner & Feig, 2014; Updegrove et al., 2016).

Generally, the proximal face preferentially binds to U-rich RNA sequences, such as the poly(U) tracts that are preceded or followed by a hairpin structure present at the 3’ termini, at rho-independent terminator, of most sRNAs, or sometimes found in a central location of the sRNA (Faner & Feig, 2014; Schulz et al., 2017). The proximal face binds polyU sequences such that uridines are stacked adjacent to phenylalanine, in pockets between neighboring monomers around the central pore. This configuration is conserved in Hfq from Gram-negative and positive bacteria (Updegrove et al., 2016).

Generally, the distal face has high affinity to A-rich sequences, which are commonly found in the 5’ untranslated regions (UTR) of mRNAs (Schulz et al., 2017). RNA contacts of the distal face are more varied than those on the proximal face (Updegrove et al., 2016). It was observed that in E. coli the distal site of each Hfq subunit can accommodate a triplet of RNA nucleotides (ARN or AAN), where A-site binds specifically adenines, R-site can accommodate both adenine and guanine with preference for A, while the N-site can be any nucleotide as it points away from Hfq towards the solvent (Schulz et al., 2017). However, in Staphylococcus aureus the distal site binds a RL motif, where R is a purine specific and L is a non-specific linker (Faner & Feig, 2014). Also, studies have shown that some sRNAs also have A-rich sequences that allow them to bind the distal surface (Updegrove et al., 2016).

The lateral site has a accessory role, providing a secondary binding site for UA-rich sequences in sRNAs (Updegrove et al., 2016; Schulz et al., 2017)

The role of the C-terminal domain in RNA binding remains murky, but what studies suggest is that it may bind to longer RNA molecules and/or increase interaction specificity by recognizing additional motifs within a RNA (Faner & Feig, 2014).

==Evolutional Conservation==

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The hfq of different bacteria include an evolutionarily conserved core consisting of amino acid residues 7–66 and has a C terminal tail which diverge significantly in length and sequence[2]. This C terminal tail is associated with the interaction with some sRnas in the protein[1].

Some studies show that this tail is flexible and have disordered regions which can facilitate intermolecular interactions. This disorder appears to provide a moiety who act like a bridge connecting diverse RNA molecules that could be followed by stable accommodation of the substrate at the distal site at the poliA binding motifs.[2]

The Sm and Lsm proteins are present in members of the Eukarya, Archaea and Bacteria domains, suggesting that this family may have evolved from a early ancestral (Schumacher et al., 2002; Wilusz & Wilusz, 2005). The Sm proteins contain two conserved regions termed the Sm1 and Sm2 motifs, which are separated by a not conserved region, neither in sequence nor in length, named variable region (Schumacher et al., 2002). There are two structures properties set Hfq apart from the others Sm proteins (Schumacher et al., 2002). First, the bacteria Hfq, unlike others described Sm proteins that usually form a heteroheptameric ring structure, oligomerizes to form a homohexameric structure (Wilusz & Wilusz, 2005). Secondly, Hfq variable region contains only a very short loop, whereas in other Sm proteins variable region consists of a long loop and also the β-strands β3 and β4 are extended to form a longer antiparallel sheet (Schumacher et al., 2002).

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@@ Line 27: / Line 27: @@
 The distal face binds to diverse A-rich sequences in mRNAs and SRNAs. Studies have demonstrade that an A-rich motif is critical for Hfq-mediated regulation.
 Rim binds to UA-rich sequences. This kind of bind improve the interaction of the HFQ with the RNAs
+==RNA binding sites==
+The ring-like architecture of the Hfq exposes two well characterized RNA binding sites referred to as “proximal”, representing the surface on which the amino (N)-terminal α-helix is exposed, and “distal” face, corresponding to the opposite surface of the proximal (Vogel & Luisi, 2011; Updegrove et al., 2016). In addition, recently studies have shown the presence of other two binding sites referred to as “lateral” or “rim” face, corresponding to the outer ring of the ring-like structure, and the carboxy (C)-terminal tail (Faner & Feig, 2014; Updegrove et al., 2016).
+Generally, the proximal face preferentially binds to U-rich RNA sequences, such as the poly(U) tracts that are preceded or followed by a hairpin structure present at the 3’ termini, at rho-independent terminator, of most sRNAs, or sometimes found in a central location of the sRNA (Faner & Feig, 2014; Schulz et al., 2017). The proximal face binds polyU sequences such that uridines are stacked adjacent to phenylalanine, in pockets between neighboring monomers around the central pore. This configuration is conserved in Hfq from Gram-negative and positive bacteria (Updegrove et al., 2016).
+Generally, the distal face has high affinity to A-rich sequences, which are commonly found in the 5’ untranslated regions (UTR) of mRNAs (Schulz et al., 2017). RNA contacts of the distal face are more varied than those on the proximal face  (Updegrove et al., 2016). It was observed that in E. coli the distal site of each Hfq subunit can accommodate a triplet of RNA nucleotides (ARN or AAN), where A-site binds specifically adenines, R-site can accommodate both adenine and guanine with preference for A, while the N-site can be any nucleotide as it points away from Hfq towards the solvent (Schulz et al., 2017). However, in Staphylococcus aureus the distal site binds a RL motif, where R is a purine specific and L is a non-specific linker (Faner & Feig, 2014). Also, studies have shown that some sRNAs also have A-rich sequences that allow them to bind the distal surface (Updegrove et al., 2016).
+The lateral site has a accessory role, providing a secondary binding site for UA-rich sequences in sRNAs (Updegrove et al., 2016; Schulz et al., 2017)
+The role of the C-terminal domain in RNA binding remains murky, but what studies suggest is that it may bind to longer RNA molecules and/or increase interaction specificity by recognizing additional motifs within a RNA (Faner & Feig, 2014).
 ==Evolutional Conservation==
@@ Line 32: / Line 43: @@
 The hfq of different bacteria include an evolutionarily conserved core consisting of amino acid residues 7–66 and has a C terminal tail which diverge significantly in length and sequence[2]. This C terminal tail is associated with the interaction with some sRnas in the protein[1].
 Some studies show that this tail is flexible and have disordered regions which can facilitate intermolecular interactions. This disorder appears to provide a moiety who act like a bridge connecting diverse RNA molecules that could be followed by stable accommodation of the substrate at the distal site at the poliA binding motifs.[2]
+The Sm and Lsm proteins are present in members of the Eukarya, Archaea and Bacteria domains, suggesting that this family may have evolved from a early ancestral (Schumacher et al., 2002; Wilusz & Wilusz, 2005). The Sm proteins contain two conserved regions termed the Sm1 and Sm2 motifs, which are separated by a not conserved region, neither in sequence nor in length, named variable region (Schumacher et al., 2002). There are two structures properties set Hfq apart from the others Sm proteins (Schumacher et al., 2002). First, the bacteria Hfq, unlike others described Sm proteins that usually form a heteroheptameric ring structure, oligomerizes to form a homohexameric structure (Wilusz & Wilusz, 2005). Secondly, Hfq variable region contains only a very short loop, whereas in other Sm proteins variable region consists of a long loop and also the β-strands β3 and β4 are extended to form a longer antiparallel sheet (Schumacher et al., 2002).