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Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein.

Kellner JN, Meinhart A - Acta Crystallogr F Struct Biol Commun (2015)

Bottom Line: Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein-protein interaction surface.The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein.By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.

ABSTRACT
The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein-protein interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein-protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

No MeSH data available.


Related in: MedlinePlus

Structural comparison of hDSPRY (green) with the SPRY domain of Ash2L (red; PDB entry 3toj; Chen et al., 2012 ▸) using the DALI server (Holm & Rosenström, 2010 ▸). Regions that show most significant structural differences are indicated by intense colour shading and are marked by grey circles. The 44-residue loop of Ash2L that is not resolved in the crystal structures is marked with a red circle. Loop D is highlighted in purple.
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fig4: Structural comparison of hDSPRY (green) with the SPRY domain of Ash2L (red; PDB entry 3toj; Chen et al., 2012 ▸) using the DALI server (Holm & Rosenström, 2010 ▸). Regions that show most significant structural differences are indicated by intense colour shading and are marked by grey circles. The 44-residue loop of Ash2L that is not resolved in the crystal structures is marked with a red circle. Loop D is highlighted in purple.

Mentions: Whereas the core structures of hDSPRY and Ash2L SPRY are structurally very similar [besides minor differences in length in the loop regions between β3 and β4 (three residues) and between β6 and β7 (three residues) and in loop D (three residues)], hDSPRY does not harbour extensive loop insertions that are comparable in length to the loop insertions in Ash2L SPRY (Fig. 4 ▸). The longest loop observed in hDSPRY contains 23 residues and connects β-strands β14 and β15 at the C-terminus. However, a large 44-residue loop insertion connects β-strands β11 and β12 in Ash2L SPRY (Chen et al., 2012 ▸). Moreover, in Bre2, a homologue of Ash2L from Saccharomyces cerevisiae, a 120-residue loop insertion in this region has been described (Chen et al., 2012 ▸). In contrast, this loop is formed by only a four-residue loop in hDSPRY.


Structure of the SPRY domain of the human RNA helicase DDX1, a putative interaction platform within a DEAD-box protein.

Kellner JN, Meinhart A - Acta Crystallogr F Struct Biol Commun (2015)

Structural comparison of hDSPRY (green) with the SPRY domain of Ash2L (red; PDB entry 3toj; Chen et al., 2012 ▸) using the DALI server (Holm & Rosenström, 2010 ▸). Regions that show most significant structural differences are indicated by intense colour shading and are marked by grey circles. The 44-residue loop of Ash2L that is not resolved in the crystal structures is marked with a red circle. Loop D is highlighted in purple.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555926&req=5

fig4: Structural comparison of hDSPRY (green) with the SPRY domain of Ash2L (red; PDB entry 3toj; Chen et al., 2012 ▸) using the DALI server (Holm & Rosenström, 2010 ▸). Regions that show most significant structural differences are indicated by intense colour shading and are marked by grey circles. The 44-residue loop of Ash2L that is not resolved in the crystal structures is marked with a red circle. Loop D is highlighted in purple.
Mentions: Whereas the core structures of hDSPRY and Ash2L SPRY are structurally very similar [besides minor differences in length in the loop regions between β3 and β4 (three residues) and between β6 and β7 (three residues) and in loop D (three residues)], hDSPRY does not harbour extensive loop insertions that are comparable in length to the loop insertions in Ash2L SPRY (Fig. 4 ▸). The longest loop observed in hDSPRY contains 23 residues and connects β-strands β14 and β15 at the C-terminus. However, a large 44-residue loop insertion connects β-strands β11 and β12 in Ash2L SPRY (Chen et al., 2012 ▸). Moreover, in Bre2, a homologue of Ash2L from Saccharomyces cerevisiae, a 120-residue loop insertion in this region has been described (Chen et al., 2012 ▸). In contrast, this loop is formed by only a four-residue loop in hDSPRY.

Bottom Line: Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein-protein interaction surface.The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein.By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.

ABSTRACT
The human RNA helicase DDX1 in the DEAD-box family plays an important role in RNA processing and has been associated with HIV-1 replication and tumour progression. Whereas previously described DEAD-box proteins have a structurally conserved core, DDX1 shows a unique structural feature: a large SPRY-domain insertion in its RecA-like consensus fold. SPRY domains are known to function as protein-protein interaction platforms. Here, the crystal structure of the SPRY domain of human DDX1 (hDSPRY) is reported at 2.0 Å resolution. The structure reveals two layers of concave, antiparallel β-sheets that stack onto each other and a third β-sheet beneath the β-sandwich. A comparison with SPRY-domain structures from other eukaryotic proteins showed that the general β-sandwich fold is conserved; however, differences were detected in the loop regions, which were identified in other SPRY domains to be essential for interaction with cognate partners. In contrast, in hDSPRY these loop regions are not strictly conserved across species. Interestingly, though, a conserved patch of positive surface charge is found that may replace the connecting loops as a protein-protein interaction surface. The data presented here comprise the first structural information on DDX1 and provide insights into the unique domain architecture of this DEAD-box protein. By providing the structure of a putative interaction domain of DDX1, this work will serve as a basis for further studies of the interaction network within the hetero-oligomeric complexes of DDX1 and of its recruitment to the HIV-1 Rev protein as a viral replication factor.

No MeSH data available.


Related in: MedlinePlus