Limits...
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.


The structure of LmTBCC-C. (A) A ribbon diagram of the fold, colored blue to red from N-terminus to C-terminus. Helix α1, is obscured behind the β-helix structure in this orientation. (B) The tyrosine ladder and a nearby tryptophan (green C atoms) and stabilizing hydrogen bonding interactions (purple dashed lines) formed with the extended C-terminal residues (yellow C atoms). A water molecule is depicted as a cyan sphere, N and O atoms are colored blue and red respectively (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4539340&req=5

fig0005: The structure of LmTBCC-C. (A) A ribbon diagram of the fold, colored blue to red from N-terminus to C-terminus. Helix α1, is obscured behind the β-helix structure in this orientation. (B) The tyrosine ladder and a nearby tryptophan (green C atoms) and stabilizing hydrogen bonding interactions (purple dashed lines) formed with the extended C-terminal residues (yellow C atoms). A water molecule is depicted as a cyan sphere, N and O atoms are colored blue and red respectively (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).

Mentions: The N-terminal segment, residues 158–242, forms a right-handed parallel β-helix barrel consisting of five coils or layers. The helical barrel is shaped as an approximate triangular prism, with faces and strands labeled A, B, C (Fig. 1A). The sides are about 20 × 10 × 20 Å with height approaching 25 Å. Three short β-strands, A and C between four and six residues in length and B only 3 residues, together form each layer of the β-helix. This β-helix structure is classified as a CARP domain, identified in cyclase-associated proteins and X-linked retinitis pigmentosa 2 gene products (http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=CARP). The rest of the polypeptide is catalogued as the TBCC domain [14] but it forms an extended structure, not at all domain-like, mainly positioned over one side of the β-helix, the C-face. This section exits the β-helix, drops down (α1) then loops up (α2, α3) and over to place β6 as a cap of the β-helix (Fig. 1A). There are numerous interactions involving hydrogen bonds and van der Waals forces formed between residues in this extended segment and those on the β-helix, including a tyrosine “ladder” composed of Tyr188, Tyr207 and Tyr224, to stabilize the fold. These interactions involve main chain and side chain groups. The arrangement of the three tyrosine residues, together with some of the stabilizing hydrogen bonding interactions, is depicted in Fig. 1B. In addition a significant hydrophobic core formed by aromatic residues (Phe170, Trp226, Tyr244, Trp247, Trp267, Phe316) help to position the α-helical loop onto the C-face (not shown). The polypeptide crosses over the top of the β-helix then drops down and the C-terminal region is tucked under the cylindricαl structure interacting with the N-terminal residues. The overall result is that the so-called “TBCC domain” is actually an extended structure that forms a shield covering one side of the molecule leaving another to potentially interact with binding partners. The extended conformation and overall structure of residues 243–355 suggests this is not in itself a bone fide domain but rather contributes to an overall C-terminal domain.


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)

The structure of LmTBCC-C. (A) A ribbon diagram of the fold, colored blue to red from N-terminus to C-terminus. Helix α1, is obscured behind the β-helix structure in this orientation. (B) The tyrosine ladder and a nearby tryptophan (green C atoms) and stabilizing hydrogen bonding interactions (purple dashed lines) formed with the extended C-terminal residues (yellow C atoms). A water molecule is depicted as a cyan sphere, N and O atoms are colored blue and red respectively (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539340&req=5

fig0005: The structure of LmTBCC-C. (A) A ribbon diagram of the fold, colored blue to red from N-terminus to C-terminus. Helix α1, is obscured behind the β-helix structure in this orientation. (B) The tyrosine ladder and a nearby tryptophan (green C atoms) and stabilizing hydrogen bonding interactions (purple dashed lines) formed with the extended C-terminal residues (yellow C atoms). A water molecule is depicted as a cyan sphere, N and O atoms are colored blue and red respectively (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).
Mentions: The N-terminal segment, residues 158–242, forms a right-handed parallel β-helix barrel consisting of five coils or layers. The helical barrel is shaped as an approximate triangular prism, with faces and strands labeled A, B, C (Fig. 1A). The sides are about 20 × 10 × 20 Å with height approaching 25 Å. Three short β-strands, A and C between four and six residues in length and B only 3 residues, together form each layer of the β-helix. This β-helix structure is classified as a CARP domain, identified in cyclase-associated proteins and X-linked retinitis pigmentosa 2 gene products (http://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=CARP). The rest of the polypeptide is catalogued as the TBCC domain [14] but it forms an extended structure, not at all domain-like, mainly positioned over one side of the β-helix, the C-face. This section exits the β-helix, drops down (α1) then loops up (α2, α3) and over to place β6 as a cap of the β-helix (Fig. 1A). There are numerous interactions involving hydrogen bonds and van der Waals forces formed between residues in this extended segment and those on the β-helix, including a tyrosine “ladder” composed of Tyr188, Tyr207 and Tyr224, to stabilize the fold. These interactions involve main chain and side chain groups. The arrangement of the three tyrosine residues, together with some of the stabilizing hydrogen bonding interactions, is depicted in Fig. 1B. In addition a significant hydrophobic core formed by aromatic residues (Phe170, Trp226, Tyr244, Trp247, Trp267, Phe316) help to position the α-helical loop onto the C-face (not shown). The polypeptide crosses over the top of the β-helix then drops down and the C-terminal region is tucked under the cylindricαl structure interacting with the N-terminal residues. The overall result is that the so-called “TBCC domain” is actually an extended structure that forms a shield covering one side of the molecule leaving another to potentially interact with binding partners. The extended conformation and overall structure of residues 243–355 suggests this is not in itself a bone fide domain but rather contributes to an overall C-terminal domain.

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.