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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 complex between the core domain of HspBP1 and the Hsp70 ATPase domain, an example of the change in the position of interface residues (stick representation; red in the B form and blue in the U form). Protein chains are shown in cartoon representation in green for the B form (PDB entry 1xqs) and in pink for the U form (PDB entry 1xqr) of the core domain of HspBP1 (Shomura et al., 2005 ▸) containing the labelled interface residues; the other component (the Hsp70 ATPase domain) in the B form is shown in cyan. ΔASA = −175 Å2 and δA = −10%. The ΔASA values for the interface atoms of the residues shown are −43 Å2 for Arg217, −20 Å2 for Glu218 and −16 Å2 for Phe210.
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fig2: The complex between the core domain of HspBP1 and the Hsp70 ATPase domain, an example of the change in the position of interface residues (stick representation; red in the B form and blue in the U form). Protein chains are shown in cartoon representation in green for the B form (PDB entry 1xqs) and in pink for the U form (PDB entry 1xqr) of the core domain of HspBP1 (Shomura et al., 2005 ▸) containing the labelled interface residues; the other component (the Hsp70 ATPase domain) in the B form is shown in cyan. ΔASA = −175 Å2 and δA = −10%. The ΔASA values for the interface atoms of the residues shown are −43 Å2 for Arg217, −20 Å2 for Glu218 and −16 Å2 for Phe210.

Mentions: While the majority of complexes show an increase in ASA, 31% (88 of the 281 components) have a negative δA value, indicating that the interface atoms are pulled back into the structure to facilitate the interaction with the incoming partner molecule: a ‘partner accommodation’ effect. Fig. 2 ▸ shows such an example with a δA value (−10%) from the opposite side of the distribution. It is seen that for the core domain of the HspBP1 protein the effect of binding has been to pull the interface atoms, which were extended into the solvent in the U form, towards itself to allow a closer approach by the partner molecule (the Hsp70 ATPase domain). While the two component contributions in the complex are weakly correlated (Fig. 3 ▸), we note that the proportions of complexes in which the ΔASA contributions of the two partner proteins are both positive (65 complexes; 47%), both negative (15 cases; 11%) and mixed positive and negative (57 complexes; 42%) are consistent with a simple statistical model of independent component contributions (p2+ = 47%, p2− = 10% and 2p+p− = 43% for p+ = 0.69 and p− = 0.31). Thus, the ‘partner accommodation effect’ does not usually operate simultaneously on both components, and complex formation is usually accompanied by the ‘partner attraction effect’. ΔASA has a poor correlation with interface r.m.s.d. and BSA (Supplementary Fig. S2), indicating it to be essentially independent of the size of the interface or the root-mean-square deviation of the interface atoms.


Changes in protein structure at the interface accompanying complex formation.

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

The complex between the core domain of HspBP1 and the Hsp70 ATPase domain, an example of the change in the position of interface residues (stick representation; red in the B form and blue in the U form). Protein chains are shown in cartoon representation in green for the B form (PDB entry 1xqs) and in pink for the U form (PDB entry 1xqr) of the core domain of HspBP1 (Shomura et al., 2005 ▸) containing the labelled interface residues; the other component (the Hsp70 ATPase domain) in the B form is shown in cyan. ΔASA = −175 Å2 and δA = −10%. The ΔASA values for the interface atoms of the residues shown are −43 Å2 for Arg217, −20 Å2 for Glu218 and −16 Å2 for Phe210.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: The complex between the core domain of HspBP1 and the Hsp70 ATPase domain, an example of the change in the position of interface residues (stick representation; red in the B form and blue in the U form). Protein chains are shown in cartoon representation in green for the B form (PDB entry 1xqs) and in pink for the U form (PDB entry 1xqr) of the core domain of HspBP1 (Shomura et al., 2005 ▸) containing the labelled interface residues; the other component (the Hsp70 ATPase domain) in the B form is shown in cyan. ΔASA = −175 Å2 and δA = −10%. The ΔASA values for the interface atoms of the residues shown are −43 Å2 for Arg217, −20 Å2 for Glu218 and −16 Å2 for Phe210.
Mentions: While the majority of complexes show an increase in ASA, 31% (88 of the 281 components) have a negative δA value, indicating that the interface atoms are pulled back into the structure to facilitate the interaction with the incoming partner molecule: a ‘partner accommodation’ effect. Fig. 2 ▸ shows such an example with a δA value (−10%) from the opposite side of the distribution. It is seen that for the core domain of the HspBP1 protein the effect of binding has been to pull the interface atoms, which were extended into the solvent in the U form, towards itself to allow a closer approach by the partner molecule (the Hsp70 ATPase domain). While the two component contributions in the complex are weakly correlated (Fig. 3 ▸), we note that the proportions of complexes in which the ΔASA contributions of the two partner proteins are both positive (65 complexes; 47%), both negative (15 cases; 11%) and mixed positive and negative (57 complexes; 42%) are consistent with a simple statistical model of independent component contributions (p2+ = 47%, p2− = 10% and 2p+p− = 43% for p+ = 0.69 and p− = 0.31). Thus, the ‘partner accommodation effect’ does not usually operate simultaneously on both components, and complex formation is usually accompanied by the ‘partner attraction effect’. ΔASA has a poor correlation with interface r.m.s.d. and BSA (Supplementary Fig. S2), indicating it to be essentially independent of the size of the interface or the root-mean-square deviation of the interface atoms.

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.