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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.


Euclidean distances involving B factors (a) between interface and surface regions (enumerated in Supplementary Table S3) and (b) between interface rim and core regions (Supplementary Table S4) in the U and B states.
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fig8: Euclidean distances involving B factors (a) between interface and surface regions (enumerated in Supplementary Table S3) and (b) between interface rim and core regions (Supplementary Table S4) in the U and B states.

Mentions: The scaled mean B factor of the backbone atoms C, Cα, O and N (along with Cβ for non-Gly residues) were calculated along with the average values for each residue type in the interface and the surface regions for both the U and B states. As expected, the average B factor was observed to be greater for the surface compared with the interface in the B structures (P value < 2 × 10−16; Supplementary Table S3, Fig. 8 ▸a). Indeed, the normalized B factors for all of the residues in the interface are negative (below the average value for all of the residues in the structure). In contrast, in the unbound structures the interface residues mostly have positive values and, as expected, the values are higher than those observed in the bound interface. Thus, on going from the the U state to the B state the interface residues exhibit a drastic reduction in B factor. Although the changes are not as strong, overall the opposite trend was observed for the surface residues (P value = 0.04). Again applying a Euclidean metric, here defined using the average B factors of amino-acid residues in the two regions of the protein structures and in the two states (Supplementary Table S3), we find that the maximum changes occur in the interface region as the complex is formed and between the interface and the surface regions in the complex. Overall, the B factors in U are quite similar between the interface and the surface. Interestingly, however, hydrophobic residues (notably the aromatic residues) tend to be more flexible at the interface compared with the surface in the U state, while the opposite seems to be the case for polar residues. Grouping Ile, Leu, Met, Phe, Trp and Tyr as nonpolar and Arg, Asn, Cys, Gln, Glu, Gly, His, Lys, Ser and Thr as polar, the difference in B factors is significant (the P values are 0.05 and 0.048, respectively). It has been noted that the δA values are higher (>4%) for all of the nonpolar residue types (Chakravarty et al., 2013 ▸). The higher flexibility in the U state of the nonpolar residues in the region that would constitute the interface (in B) may thus predispose them to conformational changes accompanying complex formation.


Changes in protein structure at the interface accompanying complex formation.

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

Euclidean distances involving B factors (a) between interface and surface regions (enumerated in Supplementary Table S3) and (b) between interface rim and core regions (Supplementary Table S4) in the U and B states.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Euclidean distances involving B factors (a) between interface and surface regions (enumerated in Supplementary Table S3) and (b) between interface rim and core regions (Supplementary Table S4) in the U and B states.
Mentions: The scaled mean B factor of the backbone atoms C, Cα, O and N (along with Cβ for non-Gly residues) were calculated along with the average values for each residue type in the interface and the surface regions for both the U and B states. As expected, the average B factor was observed to be greater for the surface compared with the interface in the B structures (P value < 2 × 10−16; Supplementary Table S3, Fig. 8 ▸a). Indeed, the normalized B factors for all of the residues in the interface are negative (below the average value for all of the residues in the structure). In contrast, in the unbound structures the interface residues mostly have positive values and, as expected, the values are higher than those observed in the bound interface. Thus, on going from the the U state to the B state the interface residues exhibit a drastic reduction in B factor. Although the changes are not as strong, overall the opposite trend was observed for the surface residues (P value = 0.04). Again applying a Euclidean metric, here defined using the average B factors of amino-acid residues in the two regions of the protein structures and in the two states (Supplementary Table S3), we find that the maximum changes occur in the interface region as the complex is formed and between the interface and the surface regions in the complex. Overall, the B factors in U are quite similar between the interface and the surface. Interestingly, however, hydrophobic residues (notably the aromatic residues) tend to be more flexible at the interface compared with the surface in the U state, while the opposite seems to be the case for polar residues. Grouping Ile, Leu, Met, Phe, Trp and Tyr as nonpolar and Arg, Asn, Cys, Gln, Glu, Gly, His, Lys, Ser and Thr as polar, the difference in B factors is significant (the P values are 0.05 and 0.048, respectively). It has been noted that the δA values are higher (>4%) for all of the nonpolar residue types (Chakravarty et al., 2013 ▸). The higher flexibility in the U state of the nonpolar residues in the region that would constitute the interface (in B) may thus predispose them to conformational changes accompanying complex formation.

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.