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Changes in protein structure at the interface accompanying complex formation.

Chakravarty D, Janin J, Robert CH, Chakrabarti P - IUCrJ (2015)

Bottom Line: It is found that the interface atoms optimize contacts with the atoms in the partner protein, which leads to an increase in their ASA in the bound interface in the majority (69%) of the proteins when compared with the unbound interface, and this is independent of the root-mean-square deviation between the U and B forms.A reduction in flexibility during complex formation is reflected in the decrease in B factors of the interface residues on going from the U form to the B form.There is, however, no distinction in flexibility between the interface and the surface in the monomeric structure, thereby highlighting the potential problem of using B factors for the prediction of binding sites in the unbound form for docking another protein. 16% of the proteins have missing (disordered) residues in the U form which are observed (ordered) in the B form, mostly with an irregular conformation; the data set also shows differences in the composition of interface and non-interface residues in the disordered polypeptide segments as well as differences in their surface burial.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Bose Institute , P-1/12 CIT Scheme VIIM, Kolkata 700 054, India.

ABSTRACT
Protein interactions are essential in all biological processes. The changes brought about in the structure when a free component forms a complex with another molecule need to be characterized for a proper understanding of molecular recognition as well as for the successful implementation of docking algorithms. Here, unbound (U) and bound (B) forms of protein structures from the Protein-Protein Interaction Affinity Database are compared in order to enumerate the changes that occur at the interface atoms/residues in terms of the solvent-accessible surface area (ASA), secondary structure, temperature factors (B factors) and disorder-to-order transitions. It is found that the interface atoms optimize contacts with the atoms in the partner protein, which leads to an increase in their ASA in the bound interface in the majority (69%) of the proteins when compared with the unbound interface, and this is independent of the root-mean-square deviation between the U and B forms. Changes in secondary structure during the transition indicate a likely extension of helices and strands at the expense of turns and coils. A reduction in flexibility during complex formation is reflected in the decrease in B factors of the interface residues on going from the U form to the B form. There is, however, no distinction in flexibility between the interface and the surface in the monomeric structure, thereby highlighting the potential problem of using B factors for the prediction of binding sites in the unbound form for docking another protein. 16% of the proteins have missing (disordered) residues in the U form which are observed (ordered) in the B form, mostly with an irregular conformation; the data set also shows differences in the composition of interface and non-interface residues in the disordered polypeptide segments as well as differences in their surface burial.

No MeSH data available.


The structure of the interface formed in human tissue inhibitor of metalloproteinases 2 when it forms a complex with type IV collagenase (PDB entry 1gxd; Morgunova et al., 2002 ▸); the inhibitor is denoted in cyan and the enzyme in violet. Surface representations of the proteins are displayed. The U state (PDB entry 1br9; Tuuttila et al., 1998 ▸) is not shown here. The interface residues are split into two categories: the residues missing in the unbound structure are in blue and those seen in both the U and B forms are in orange. The missing segment (183–192) is composed of both non-interface residues (shown in red) and interface residues (blue). The missing residues contribute 504 Å2 to the BSA of 1268 Å2 of the inhibitor.
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fig6: The structure of the interface formed in human tissue inhibitor of metalloproteinases 2 when it forms a complex with type IV collagenase (PDB entry 1gxd; Morgunova et al., 2002 ▸); the inhibitor is denoted in cyan and the enzyme in violet. Surface representations of the proteins are displayed. The U state (PDB entry 1br9; Tuuttila et al., 1998 ▸) is not shown here. The interface residues are split into two categories: the residues missing in the unbound structure are in blue and those seen in both the U and B forms are in orange. The missing segment (183–192) is composed of both non-interface residues (shown in red) and interface residues (blue). The missing residues contribute 504 Å2 to the BSA of 1268 Å2 of the inhibitor.

Mentions: The total interface in a complex is made up of contributions from both components, the BSA values of which are generally similar but not equal. It is of interest to study the contribution of a specific residue not only to the BSA of its own component (‘parent’), but also to that of the partner component owing to their interaction. Overall, the missing residues in a given component contribute 155 ± 270 Å2 to the BSA of the parent and nearly the same (156 ± 246 Å2) to that of the partner. However, in those cases for which missing residues contributed more than 200 Å2 to the parent (13 structures, missing nine residues per structure on average), the contribution to the partner was smaller on average by 34 ± 50 Å2. It may be mentioned in connection that the BSA values of the interacting proteins are normally nearly identical; in the case of protease–inhibitor complexes, however, the convex nature of the inhibitor surface fitting into the concave active site results in its BSA exceeding that of the enzyme in the ratio 54:46 (Lo Conte et al., 1999 ▸). Figs. 6 ▸ and 7 ▸ provide two illustrations of a missing segment and the structure (mostly of irregular conformation) adopted in the B form. The example in Fig. 6 ▸ is a case in which the gain in BSA from missing residues in the parent molecule exceeds that in the partner by 139 Å2. The asymmetric nature of the BSA values for the two sides is owing to the better fitting of the disordered residues into the grooves and crevices of the more ordered interacting partner. Favourable interactions arising from the burial of these residues should also help to compensate for the entropic loss of ordering them.


Changes in protein structure at the interface accompanying complex formation.

Chakravarty D, Janin J, Robert CH, Chakrabarti P - IUCrJ (2015)

The structure of the interface formed in human tissue inhibitor of metalloproteinases 2 when it forms a complex with type IV collagenase (PDB entry 1gxd; Morgunova et al., 2002 ▸); the inhibitor is denoted in cyan and the enzyme in violet. Surface representations of the proteins are displayed. The U state (PDB entry 1br9; Tuuttila et al., 1998 ▸) is not shown here. The interface residues are split into two categories: the residues missing in the unbound structure are in blue and those seen in both the U and B forms are in orange. The missing segment (183–192) is composed of both non-interface residues (shown in red) and interface residues (blue). The missing residues contribute 504 Å2 to the BSA of 1268 Å2 of the inhibitor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645109&req=5

fig6: The structure of the interface formed in human tissue inhibitor of metalloproteinases 2 when it forms a complex with type IV collagenase (PDB entry 1gxd; Morgunova et al., 2002 ▸); the inhibitor is denoted in cyan and the enzyme in violet. Surface representations of the proteins are displayed. The U state (PDB entry 1br9; Tuuttila et al., 1998 ▸) is not shown here. The interface residues are split into two categories: the residues missing in the unbound structure are in blue and those seen in both the U and B forms are in orange. The missing segment (183–192) is composed of both non-interface residues (shown in red) and interface residues (blue). The missing residues contribute 504 Å2 to the BSA of 1268 Å2 of the inhibitor.
Mentions: The total interface in a complex is made up of contributions from both components, the BSA values of which are generally similar but not equal. It is of interest to study the contribution of a specific residue not only to the BSA of its own component (‘parent’), but also to that of the partner component owing to their interaction. Overall, the missing residues in a given component contribute 155 ± 270 Å2 to the BSA of the parent and nearly the same (156 ± 246 Å2) to that of the partner. However, in those cases for which missing residues contributed more than 200 Å2 to the parent (13 structures, missing nine residues per structure on average), the contribution to the partner was smaller on average by 34 ± 50 Å2. It may be mentioned in connection that the BSA values of the interacting proteins are normally nearly identical; in the case of protease–inhibitor complexes, however, the convex nature of the inhibitor surface fitting into the concave active site results in its BSA exceeding that of the enzyme in the ratio 54:46 (Lo Conte et al., 1999 ▸). Figs. 6 ▸ and 7 ▸ provide two illustrations of a missing segment and the structure (mostly of irregular conformation) adopted in the B form. The example in Fig. 6 ▸ is a case in which the gain in BSA from missing residues in the parent molecule exceeds that in the partner by 139 Å2. The asymmetric nature of the BSA values for the two sides is owing to the better fitting of the disordered residues into the grooves and crevices of the more ordered interacting partner. Favourable interactions arising from the burial of these residues should also help to compensate for the entropic loss of ordering them.

Bottom Line: It is found that the interface atoms optimize contacts with the atoms in the partner protein, which leads to an increase in their ASA in the bound interface in the majority (69%) of the proteins when compared with the unbound interface, and this is independent of the root-mean-square deviation between the U and B forms.A reduction in flexibility during complex formation is reflected in the decrease in B factors of the interface residues on going from the U form to the B form.There is, however, no distinction in flexibility between the interface and the surface in the monomeric structure, thereby highlighting the potential problem of using B factors for the prediction of binding sites in the unbound form for docking another protein. 16% of the proteins have missing (disordered) residues in the U form which are observed (ordered) in the B form, mostly with an irregular conformation; the data set also shows differences in the composition of interface and non-interface residues in the disordered polypeptide segments as well as differences in their surface burial.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biochemistry, Bose Institute , P-1/12 CIT Scheme VIIM, Kolkata 700 054, India.

ABSTRACT
Protein interactions are essential in all biological processes. The changes brought about in the structure when a free component forms a complex with another molecule need to be characterized for a proper understanding of molecular recognition as well as for the successful implementation of docking algorithms. Here, unbound (U) and bound (B) forms of protein structures from the Protein-Protein Interaction Affinity Database are compared in order to enumerate the changes that occur at the interface atoms/residues in terms of the solvent-accessible surface area (ASA), secondary structure, temperature factors (B factors) and disorder-to-order transitions. It is found that the interface atoms optimize contacts with the atoms in the partner protein, which leads to an increase in their ASA in the bound interface in the majority (69%) of the proteins when compared with the unbound interface, and this is independent of the root-mean-square deviation between the U and B forms. Changes in secondary structure during the transition indicate a likely extension of helices and strands at the expense of turns and coils. A reduction in flexibility during complex formation is reflected in the decrease in B factors of the interface residues on going from the U form to the B form. There is, however, no distinction in flexibility between the interface and the surface in the monomeric structure, thereby highlighting the potential problem of using B factors for the prediction of binding sites in the unbound form for docking another protein. 16% of the proteins have missing (disordered) residues in the U form which are observed (ordered) in the B form, mostly with an irregular conformation; the data set also shows differences in the composition of interface and non-interface residues in the disordered polypeptide segments as well as differences in their surface burial.

No MeSH data available.