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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.


Secondary-structural changes during the U-to-B transition. (a) The change in percentage composition between the two states (B – U) for the secondary-structural elements (helix, H; strand, S; turn, T; irregular, C) for the cases with Euclidean distances between the two sets of compositions of >5. (b) Percentage composition of 224 residues showing the C/T to H/S transition, categorized into the extension of an already existing helix/strand (EH and ES) or the formation of a new helix/strand (FH and FS).
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fig4: Secondary-structural changes during the U-to-B transition. (a) The change in percentage composition between the two states (B – U) for the secondary-structural elements (helix, H; strand, S; turn, T; irregular, C) for the cases with Euclidean distances between the two sets of compositions of >5. (b) Percentage composition of 224 residues showing the C/T to H/S transition, categorized into the extension of an already existing helix/strand (EH and ES) or the formation of a new helix/strand (FH and FS).

Mentions: The change in the percentage composition of secondary-structural elements for the U to B transition was calculated, and 76% cases (213 of 281) showed some change. To restrict the analysis to meaningful changes, we computed the Euclidean distance (D) between the compositions of the four structural elements. The average value of D is 5.6 (±5.4), and we used structural pairs with D > 5 (134 cases) to understand the structural changes accompanying complex formation (Fig. 4 ▸a) [the histograms for D > 10 and D > 15 (Supplementary Figs. S3a and S3b) look very similar]. It can be seen that complex formation leads to an increase in helical and strand content (especially the former) at the expense of irregular (and to some extent turn) regions in the structure. 91 structural pairs show an irregular/turn (C/T) to helix/strand (H/S) transition, affecting 75 helices and 81 strands, corresponding to 34% of helices and 38% of strands, respectively, of these structural elements in the B form of the proteins. These cases have an average D value of 7.8 ± 4.9, with 224 residues changing conformation. The majority of these (161 cases) are involved in the extension of an already existing helix or strand (Fig. 4 ▸b). Cases of extension seem to marginally favour the C-terminal end of helices and the N-terminal end of strands (Supplementary Fig. S3c). The residues located in the interface core (108 of 224; 48%) and rim (52%) are affected equally, among which Arg, Glu, Ser and Tyr are those more frequently involved in the transition from C/T to H/S. Two representative examples showing secondary-structural changes are presented in Fig. 5 ▸.


Changes in protein structure at the interface accompanying complex formation.

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

Secondary-structural changes during the U-to-B transition. (a) The change in percentage composition between the two states (B – U) for the secondary-structural elements (helix, H; strand, S; turn, T; irregular, C) for the cases with Euclidean distances between the two sets of compositions of >5. (b) Percentage composition of 224 residues showing the C/T to H/S transition, categorized into the extension of an already existing helix/strand (EH and ES) or the formation of a new helix/strand (FH and FS).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Secondary-structural changes during the U-to-B transition. (a) The change in percentage composition between the two states (B – U) for the secondary-structural elements (helix, H; strand, S; turn, T; irregular, C) for the cases with Euclidean distances between the two sets of compositions of >5. (b) Percentage composition of 224 residues showing the C/T to H/S transition, categorized into the extension of an already existing helix/strand (EH and ES) or the formation of a new helix/strand (FH and FS).
Mentions: The change in the percentage composition of secondary-structural elements for the U to B transition was calculated, and 76% cases (213 of 281) showed some change. To restrict the analysis to meaningful changes, we computed the Euclidean distance (D) between the compositions of the four structural elements. The average value of D is 5.6 (±5.4), and we used structural pairs with D > 5 (134 cases) to understand the structural changes accompanying complex formation (Fig. 4 ▸a) [the histograms for D > 10 and D > 15 (Supplementary Figs. S3a and S3b) look very similar]. It can be seen that complex formation leads to an increase in helical and strand content (especially the former) at the expense of irregular (and to some extent turn) regions in the structure. 91 structural pairs show an irregular/turn (C/T) to helix/strand (H/S) transition, affecting 75 helices and 81 strands, corresponding to 34% of helices and 38% of strands, respectively, of these structural elements in the B form of the proteins. These cases have an average D value of 7.8 ± 4.9, with 224 residues changing conformation. The majority of these (161 cases) are involved in the extension of an already existing helix or strand (Fig. 4 ▸b). Cases of extension seem to marginally favour the C-terminal end of helices and the N-terminal end of strands (Supplementary Fig. S3c). The residues located in the interface core (108 of 224; 48%) and rim (52%) are affected equally, among which Arg, Glu, Ser and Tyr are those more frequently involved in the transition from C/T to H/S. Two representative examples showing secondary-structural changes are presented in Fig. 5 ▸.

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.