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Hydration of protein-RNA recognition sites.

Barik A, Bahadur RP - Nucleic Acids Res. (2014)

Bottom Line: Majority of the waters at protein-RNA interfaces makes multiple H-bonds; however, a fraction do not make any.The preserved waters at protein-RNA interfaces make higher number of H-bonds than the other waters.Preserved waters contribute toward the affinity in protein-RNA recognition and should be carefully treated while engineering protein-RNA interfaces.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.

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Preserved interface water molecules in a protein–RNA recognition site. In the top left panel, the bound complex between ribosomal protein L1 and mRNA (2HW8) with interface waters (in red) and preserved waters (in magenta) are shown. In the top right panel, the unbound protein and the four preserved waters are shown. Protein and RNA chains are shown in gray and green color, respectively. The panels below show the conservation of four interface waters. These preserved waters making same H-bond in the bound and unbound forms of the protein.
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Figure 6: Preserved interface water molecules in a protein–RNA recognition site. In the top left panel, the bound complex between ribosomal protein L1 and mRNA (2HW8) with interface waters (in red) and preserved waters (in magenta) are shown. In the top right panel, the unbound protein and the four preserved waters are shown. Protein and RNA chains are shown in gray and green color, respectively. The panels below show the conservation of four interface waters. These preserved waters making same H-bond in the bound and unbound forms of the protein.

Mentions: Preservation of waters at the protein–RNA interfaces was identified by comparing the bound structures with their corresponding unbound structures of the protein or the RNA (refer to the ‘Materials and Methods’ section). When both protein and RNA are available in the unbound form, we considered both of them to assign preserved waters. The number of preserved waters varies from 0 to 17 in the present dataset with an average of six (∼21% of the interface waters) per interface. This low average definitely under-represents the preserved waters, since in most of the cases we found either protein or RNA in the unbound form. This is exemplified by two complexes (PDB ids: 2R8S, 1JBS), where the corresponding protein and the RNA are available in the unbound form. In both the cases, the number of preserved waters increases when we considered the bound waters in the complex along with the free form of its partners. Moreover, it should be noted that the poor assignment of the waters in the bound and the unbound crystal structures results in the lack of preserved waters. We did not find any preserved water in two interfaces with single-stranded RNA: the one with TRAP (PDB id: 1C9S), and the other with ERA (PDB id: 3IEV). Although the complex TRAP-RNA is determined with high resolution (1.9 Å), it reports 86 bound waters, of which only six are at the interface. The complex between interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) and a single-stranded RNA (PDB id: 4HOR) contains the highest number (17) of preserved waters. The X-ray structure of this complex reports 425 bound waters, of which 42 are at the interface. The helical domain of IFIT5 houses a positively charged cavity filled with interface waters (51). These cavity lining waters are also observed in the unbound structure of IFIT5 (PDB id: 4HOQ), and they remain preserved upon complexation by contributing to the optimization of the van der Waals interactions. Figure 6 shows preserved waters in the ribosomal protein L1–mRNA complex (PDB id: 2HW8). Here, we identified 24 interface waters, of which four are preserved. They make H-bonds with the same polar groups in the bound and the unbound form of the protein. In the entire dataset, we found 266 preserved waters, which is equivalent to 5.2 per 1000 Å2 of B. This density varies among the different classes: the lowest in interfaces with tRNA and the highest in interfaces with single-stranded RNA. Moreover, we found that the preserved waters make an average of 2.5 H-bonds compared to the other interface waters, which make only 1.9.


Hydration of protein-RNA recognition sites.

Barik A, Bahadur RP - Nucleic Acids Res. (2014)

Preserved interface water molecules in a protein–RNA recognition site. In the top left panel, the bound complex between ribosomal protein L1 and mRNA (2HW8) with interface waters (in red) and preserved waters (in magenta) are shown. In the top right panel, the unbound protein and the four preserved waters are shown. Protein and RNA chains are shown in gray and green color, respectively. The panels below show the conservation of four interface waters. These preserved waters making same H-bond in the bound and unbound forms of the protein.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4150782&req=5

Figure 6: Preserved interface water molecules in a protein–RNA recognition site. In the top left panel, the bound complex between ribosomal protein L1 and mRNA (2HW8) with interface waters (in red) and preserved waters (in magenta) are shown. In the top right panel, the unbound protein and the four preserved waters are shown. Protein and RNA chains are shown in gray and green color, respectively. The panels below show the conservation of four interface waters. These preserved waters making same H-bond in the bound and unbound forms of the protein.
Mentions: Preservation of waters at the protein–RNA interfaces was identified by comparing the bound structures with their corresponding unbound structures of the protein or the RNA (refer to the ‘Materials and Methods’ section). When both protein and RNA are available in the unbound form, we considered both of them to assign preserved waters. The number of preserved waters varies from 0 to 17 in the present dataset with an average of six (∼21% of the interface waters) per interface. This low average definitely under-represents the preserved waters, since in most of the cases we found either protein or RNA in the unbound form. This is exemplified by two complexes (PDB ids: 2R8S, 1JBS), where the corresponding protein and the RNA are available in the unbound form. In both the cases, the number of preserved waters increases when we considered the bound waters in the complex along with the free form of its partners. Moreover, it should be noted that the poor assignment of the waters in the bound and the unbound crystal structures results in the lack of preserved waters. We did not find any preserved water in two interfaces with single-stranded RNA: the one with TRAP (PDB id: 1C9S), and the other with ERA (PDB id: 3IEV). Although the complex TRAP-RNA is determined with high resolution (1.9 Å), it reports 86 bound waters, of which only six are at the interface. The complex between interferon-induced protein with tetratricopeptide repeats 5 (IFIT5) and a single-stranded RNA (PDB id: 4HOR) contains the highest number (17) of preserved waters. The X-ray structure of this complex reports 425 bound waters, of which 42 are at the interface. The helical domain of IFIT5 houses a positively charged cavity filled with interface waters (51). These cavity lining waters are also observed in the unbound structure of IFIT5 (PDB id: 4HOQ), and they remain preserved upon complexation by contributing to the optimization of the van der Waals interactions. Figure 6 shows preserved waters in the ribosomal protein L1–mRNA complex (PDB id: 2HW8). Here, we identified 24 interface waters, of which four are preserved. They make H-bonds with the same polar groups in the bound and the unbound form of the protein. In the entire dataset, we found 266 preserved waters, which is equivalent to 5.2 per 1000 Å2 of B. This density varies among the different classes: the lowest in interfaces with tRNA and the highest in interfaces with single-stranded RNA. Moreover, we found that the preserved waters make an average of 2.5 H-bonds compared to the other interface waters, which make only 1.9.

Bottom Line: Majority of the waters at protein-RNA interfaces makes multiple H-bonds; however, a fraction do not make any.The preserved waters at protein-RNA interfaces make higher number of H-bonds than the other waters.Preserved waters contribute toward the affinity in protein-RNA recognition and should be carefully treated while engineering protein-RNA interfaces.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.

Show MeSH
Related in: MedlinePlus