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Crystal structure of the C-terminal domain of tubulin-binding cofactor C from Leishmania major.

Barrack KL, Fyfe PK, Finney AJ, Hunter WN - Mol. Biochem. Parasitol. (2015)

Bottom Line: Although previously predicted to consist of two domains the structure is best described as a single domain dominated by a right-handed β-helix of five turns that form a triangular prism.One face of the prism is covered by the C-terminal residues leaving another face solvent exposed.Comparisons with an orthologous human GTPase activating protein match key residues involved in binding nucleotide and identify the face of the β-helix fold likely involved in interacting with the β-tubulin:GTP complex.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

No MeSH data available.


Comparison of LmTBCC-C with human RP2. (A) RP2 (blue Cα, PDB 3βh6 [19]) superimposed on LmTBCC-C (yellow Cα). The two proteins share 24% sequence identity. DALI [31] was used to inform comparison with structures in the PDB. The second domain from RP2 (residues 224–350) for which there is no similarity to LmTBCC-C has been removed for clarity. Several residues implicated in GTP binding in the RP2-ARL structure are highlighted where they remain conserved or conservatively altered in LmTBCC-C. These are labeled with the LmTBCC residue type and number, then the RP2-ARL residue type if different, and number. Residues positioned to make hydrogen bond interactions with the nucleotide from RP2 and their corresponding residues in LmTBCC-C are shown as sticks. (B) Sequence alignment of LmTBCC-C with part of human RP2 (Uniprot: O75695). The secondary structure of LmTBCC-C is shown and strictly conserved residues encased in black. Figure made with ALINE [32].
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fig0010: Comparison of LmTBCC-C with human RP2. (A) RP2 (blue Cα, PDB 3βh6 [19]) superimposed on LmTBCC-C (yellow Cα). The two proteins share 24% sequence identity. DALI [31] was used to inform comparison with structures in the PDB. The second domain from RP2 (residues 224–350) for which there is no similarity to LmTBCC-C has been removed for clarity. Several residues implicated in GTP binding in the RP2-ARL structure are highlighted where they remain conserved or conservatively altered in LmTBCC-C. These are labeled with the LmTBCC residue type and number, then the RP2-ARL residue type if different, and number. Residues positioned to make hydrogen bond interactions with the nucleotide from RP2 and their corresponding residues in LmTBCC-C are shown as sticks. (B) Sequence alignment of LmTBCC-C with part of human RP2 (Uniprot: O75695). The secondary structure of LmTBCC-C is shown and strictly conserved residues encased in black. Figure made with ALINE [32].

Mentions: The structure of the LmTBCC-C domain matches to the human retinitis pigmentosa 2 (RP2) protein with an r.m.s.d. of 2.3 Å and a sequence identity of about 25% over 139 residues (Fig. 2A). An alignment of the amino acid sequences is presented in Fig. 2B. The β-helix structures are closely related and the majority of strictly conserved residues occur on the β-strands. This extends to a similar cysteine stacking formation to that discussed above [16]. A further stack of conserved aliphatic and hydrophobic residues is positioned in the middle of βA strands 2–5. The particular arrangement of externally oriented tyrosine residues in the middle of βC strands 1–4 also creates the same tyrosine “ladder” described. These conserved features suggest they are likely important for the correct folding and stability of the β-helix fold [17].


Crystal structure of the C-terminal domain of tubulin-binding cofactor C from Leishmania major.

Barrack KL, Fyfe PK, Finney AJ, Hunter WN - Mol. Biochem. Parasitol. (2015)

Comparison of LmTBCC-C with human RP2. (A) RP2 (blue Cα, PDB 3βh6 [19]) superimposed on LmTBCC-C (yellow Cα). The two proteins share 24% sequence identity. DALI [31] was used to inform comparison with structures in the PDB. The second domain from RP2 (residues 224–350) for which there is no similarity to LmTBCC-C has been removed for clarity. Several residues implicated in GTP binding in the RP2-ARL structure are highlighted where they remain conserved or conservatively altered in LmTBCC-C. These are labeled with the LmTBCC residue type and number, then the RP2-ARL residue type if different, and number. Residues positioned to make hydrogen bond interactions with the nucleotide from RP2 and their corresponding residues in LmTBCC-C are shown as sticks. (B) Sequence alignment of LmTBCC-C with part of human RP2 (Uniprot: O75695). The secondary structure of LmTBCC-C is shown and strictly conserved residues encased in black. Figure made with ALINE [32].
© Copyright Policy - CC BY
Related In: Results  -  Collection

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fig0010: Comparison of LmTBCC-C with human RP2. (A) RP2 (blue Cα, PDB 3βh6 [19]) superimposed on LmTBCC-C (yellow Cα). The two proteins share 24% sequence identity. DALI [31] was used to inform comparison with structures in the PDB. The second domain from RP2 (residues 224–350) for which there is no similarity to LmTBCC-C has been removed for clarity. Several residues implicated in GTP binding in the RP2-ARL structure are highlighted where they remain conserved or conservatively altered in LmTBCC-C. These are labeled with the LmTBCC residue type and number, then the RP2-ARL residue type if different, and number. Residues positioned to make hydrogen bond interactions with the nucleotide from RP2 and their corresponding residues in LmTBCC-C are shown as sticks. (B) Sequence alignment of LmTBCC-C with part of human RP2 (Uniprot: O75695). The secondary structure of LmTBCC-C is shown and strictly conserved residues encased in black. Figure made with ALINE [32].
Mentions: The structure of the LmTBCC-C domain matches to the human retinitis pigmentosa 2 (RP2) protein with an r.m.s.d. of 2.3 Å and a sequence identity of about 25% over 139 residues (Fig. 2A). An alignment of the amino acid sequences is presented in Fig. 2B. The β-helix structures are closely related and the majority of strictly conserved residues occur on the β-strands. This extends to a similar cysteine stacking formation to that discussed above [16]. A further stack of conserved aliphatic and hydrophobic residues is positioned in the middle of βA strands 2–5. The particular arrangement of externally oriented tyrosine residues in the middle of βC strands 1–4 also creates the same tyrosine “ladder” described. These conserved features suggest they are likely important for the correct folding and stability of the β-helix fold [17].

Bottom Line: Although previously predicted to consist of two domains the structure is best described as a single domain dominated by a right-handed β-helix of five turns that form a triangular prism.One face of the prism is covered by the C-terminal residues leaving another face solvent exposed.Comparisons with an orthologous human GTPase activating protein match key residues involved in binding nucleotide and identify the face of the β-helix fold likely involved in interacting with the β-tubulin:GTP complex.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

No MeSH data available.