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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.


Hydrogen-bond geometries (distances shown) in α-amylase (green) and tendamistat (cyan) between His201 NE2 and Tyr820 OH for (a) the pseudo-complex and (b) the experimental complex [PDB entry 1bvn (Wiegand et al., 1995 ▸); PDB entries 1pig (Machius et al., 1996 ▸) and 1hoe (Pflugrath et al., 1986 ▸) are the U forms]. ΔASA for the participating atom and all of the interface atoms of the residues are −0.6 and −3.2 Å2, respectively, for His, and 4.2 and 15.5 Å2, respectively, for Tyr.
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fig1: Hydrogen-bond geometries (distances shown) in α-amylase (green) and tendamistat (cyan) between His201 NE2 and Tyr820 OH for (a) the pseudo-complex and (b) the experimental complex [PDB entry 1bvn (Wiegand et al., 1995 ▸); PDB entries 1pig (Machius et al., 1996 ▸) and 1hoe (Pflugrath et al., 1986 ▸) are the U forms]. ΔASA for the participating atom and all of the interface atoms of the residues are −0.6 and −3.2 Å2, respectively, for His, and 4.2 and 15.5 Å2, respectively, for Tyr.

Mentions: Previously, we had shown that on going from the U form to the B form the interface atoms undergo an increase in accessible surface area (ASA), leading to a positive δA value (Supplementary Fig. S1; mean = 3.3 ± 9.2%), which is the result of conformational changes taking place at the interface (Chakravarty et al., 2013 ▸). (As a control, we checked the variation of the ASA of free surface residues, which show only an insignificant increase, with a mean value of 0.90 ± 6.06%.) Considering the whole residue, which includes non-interface atoms, the increase can still be seen (1.3 ± 8.03%) but is smaller than that exhibited by the interface atoms alone. The ASA increase reflects what might be called a ‘partner attraction effect’: interface atoms are extended in the bound state to optimize contact with the binding partner. In addition to maximizing van der Waals interactions, the increase in the ASA of interface atoms could also be the result of optimizing interchain hydrogen-bond geometry. As a simple quantification of this, we used structures for which the combined r.m.s.d. for the U-to-B change for the two components (I_r.m.s.d. according to Kastritis et al., 2011 ▸) is <1 Å. For these 59 cases we generated the pseudo-complex by superimposing the two U forms onto the corresponding B structures. The average number of hydrogen bonds in the pseudo-complex is 3.7 ± 2.5, whereas in the real complex it is 8.0 ± 3.7, a 45% increase. An example of the local adjustment of the two U structures leading to the formation of a hydrogen bond in the complex is shown in Fig. 1 ▸: the structural rearrangement pulls out the Tyr residue such that there is a net gain in ΔASA.


Changes in protein structure at the interface accompanying complex formation.

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

Hydrogen-bond geometries (distances shown) in α-amylase (green) and tendamistat (cyan) between His201 NE2 and Tyr820 OH for (a) the pseudo-complex and (b) the experimental complex [PDB entry 1bvn (Wiegand et al., 1995 ▸); PDB entries 1pig (Machius et al., 1996 ▸) and 1hoe (Pflugrath et al., 1986 ▸) are the U forms]. ΔASA for the participating atom and all of the interface atoms of the residues are −0.6 and −3.2 Å2, respectively, for His, and 4.2 and 15.5 Å2, respectively, for Tyr.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Hydrogen-bond geometries (distances shown) in α-amylase (green) and tendamistat (cyan) between His201 NE2 and Tyr820 OH for (a) the pseudo-complex and (b) the experimental complex [PDB entry 1bvn (Wiegand et al., 1995 ▸); PDB entries 1pig (Machius et al., 1996 ▸) and 1hoe (Pflugrath et al., 1986 ▸) are the U forms]. ΔASA for the participating atom and all of the interface atoms of the residues are −0.6 and −3.2 Å2, respectively, for His, and 4.2 and 15.5 Å2, respectively, for Tyr.
Mentions: Previously, we had shown that on going from the U form to the B form the interface atoms undergo an increase in accessible surface area (ASA), leading to a positive δA value (Supplementary Fig. S1; mean = 3.3 ± 9.2%), which is the result of conformational changes taking place at the interface (Chakravarty et al., 2013 ▸). (As a control, we checked the variation of the ASA of free surface residues, which show only an insignificant increase, with a mean value of 0.90 ± 6.06%.) Considering the whole residue, which includes non-interface atoms, the increase can still be seen (1.3 ± 8.03%) but is smaller than that exhibited by the interface atoms alone. The ASA increase reflects what might be called a ‘partner attraction effect’: interface atoms are extended in the bound state to optimize contact with the binding partner. In addition to maximizing van der Waals interactions, the increase in the ASA of interface atoms could also be the result of optimizing interchain hydrogen-bond geometry. As a simple quantification of this, we used structures for which the combined r.m.s.d. for the U-to-B change for the two components (I_r.m.s.d. according to Kastritis et al., 2011 ▸) is <1 Å. For these 59 cases we generated the pseudo-complex by superimposing the two U forms onto the corresponding B structures. The average number of hydrogen bonds in the pseudo-complex is 3.7 ± 2.5, whereas in the real complex it is 8.0 ± 3.7, a 45% increase. An example of the local adjustment of the two U structures leading to the formation of a hydrogen bond in the complex is shown in Fig. 1 ▸: the structural rearrangement pulls out the Tyr residue such that there is a net gain in ΔASA.

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.