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Decomposing the space of protein quaternary structures with the interface fragment pair library.

Xie ZR, Chen J, Zhao Y, Wu Y - BMC Bioinformatics (2015)

Bottom Line: After structural-based clustering, we found that more than 90% of these interface fragment pairs can be represented by a limited number of highly abundant motifs.Our study therefore presents supportive evidences that the space of protein quaternary structures can be represented by the combination of a small set of secondary-structure-based packing at binding interfaces.Finally, after future improvements such as adding sequence profiles, we expect this new library will be useful to predict structures of unknown protein-protein interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. Zhong-Ru.Xie@einstein.yu.edu.

ABSTRACT

Background: The physical interactions between proteins constitute the basis of protein quaternary structures. They dominate many biological processes in living cells. Deciphering the structural features of interacting proteins is essential to understand their cellular functions. Similar to the space of protein tertiary structures in which discrete patterns are clearly observed on fold or sub-fold motif levels, it has been found that the space of protein quaternary structures is highly degenerate due to the packing of compact secondary structure elements at interfaces. Therefore, it is necessary to further decompose the protein quaternary structural space into a more local representation.

Results: Here we constructed an interface fragment pair library from the current structure database of protein complexes. After structural-based clustering, we found that more than 90% of these interface fragment pairs can be represented by a limited number of highly abundant motifs. These motifs were further used to guide complex assembly. A large-scale benchmark test shows that the native-like binding is highly likely in the structural ensemble of modeled protein complexes that were built through the library.

Conclusions: Our study therefore presents supportive evidences that the space of protein quaternary structures can be represented by the combination of a small set of secondary-structure-based packing at binding interfaces. Finally, after future improvements such as adding sequence profiles, we expect this new library will be useful to predict structures of unknown protein-protein interactions.

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We show some specific examples of our benchmark results. A variety of different secondary structure types are presented at the binding interfaces of these complexes. An SS motif in which two strands form hydrogen-bond-based contacts is observed in (a). A pair of helices is observed at the interface of (b). Comparatively, the complex in (c) contains a more extensive interface. The native-like binding modes were successfully reproduced in these three cases, while (d) shows an example in which we failed to assemble the proteins into a complex that is close to the native quaternary structure. The interface fragment pairs are highlighted in the modeled structural complexes. The fragments located at the interfaces of green monomers are shown in blue and the fragments located at the interfaces of red monomers are shown in yellow.
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Fig8: We show some specific examples of our benchmark results. A variety of different secondary structure types are presented at the binding interfaces of these complexes. An SS motif in which two strands form hydrogen-bond-based contacts is observed in (a). A pair of helices is observed at the interface of (b). Comparatively, the complex in (c) contains a more extensive interface. The native-like binding modes were successfully reproduced in these three cases, while (d) shows an example in which we failed to assemble the proteins into a complex that is close to the native quaternary structure. The interface fragment pairs are highlighted in the modeled structural complexes. The fragments located at the interfaces of green monomers are shown in blue and the fragments located at the interfaces of red monomers are shown in yellow.

Mentions: Some specific examples of our modeling results are shown in Figure 8. The Cα traces in red and green are the lowest RMSD structural models of assembled receptors and ligands, while their native structures are superimposed transparently by cartoon representation. The PDB id of the selected complexes, and the RMSD values between the model and the native structures are also listed in the figure. A variety of different secondary structure types are presented at the binding interfaces of these complexes. An SS motif in which two strands form hydrogen-bond-based contacts is observed in Figure 8a, while in Figure 8b, binding is achieved through interactions between a pair of helices. Comparatively, the complex in Figure 8c contains a more extensive interface. In all these three cases, the native-like binding modes exist in the structural ensemble we constructed through the interface fragment pair library. In contrast, Figure 8d shows an example in which we failed to assemble the proteins into a complex that is close to the native quaternary structure. The interface of the receptor in this complex contains a long region of disordered loop. The corresponding fragment pairs in this interface may not appear in our library, leading into the result that its native-like binding cannot be derived.Figure 8


Decomposing the space of protein quaternary structures with the interface fragment pair library.

Xie ZR, Chen J, Zhao Y, Wu Y - BMC Bioinformatics (2015)

We show some specific examples of our benchmark results. A variety of different secondary structure types are presented at the binding interfaces of these complexes. An SS motif in which two strands form hydrogen-bond-based contacts is observed in (a). A pair of helices is observed at the interface of (b). Comparatively, the complex in (c) contains a more extensive interface. The native-like binding modes were successfully reproduced in these three cases, while (d) shows an example in which we failed to assemble the proteins into a complex that is close to the native quaternary structure. The interface fragment pairs are highlighted in the modeled structural complexes. The fragments located at the interfaces of green monomers are shown in blue and the fragments located at the interfaces of red monomers are shown in yellow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4384354&req=5

Fig8: We show some specific examples of our benchmark results. A variety of different secondary structure types are presented at the binding interfaces of these complexes. An SS motif in which two strands form hydrogen-bond-based contacts is observed in (a). A pair of helices is observed at the interface of (b). Comparatively, the complex in (c) contains a more extensive interface. The native-like binding modes were successfully reproduced in these three cases, while (d) shows an example in which we failed to assemble the proteins into a complex that is close to the native quaternary structure. The interface fragment pairs are highlighted in the modeled structural complexes. The fragments located at the interfaces of green monomers are shown in blue and the fragments located at the interfaces of red monomers are shown in yellow.
Mentions: Some specific examples of our modeling results are shown in Figure 8. The Cα traces in red and green are the lowest RMSD structural models of assembled receptors and ligands, while their native structures are superimposed transparently by cartoon representation. The PDB id of the selected complexes, and the RMSD values between the model and the native structures are also listed in the figure. A variety of different secondary structure types are presented at the binding interfaces of these complexes. An SS motif in which two strands form hydrogen-bond-based contacts is observed in Figure 8a, while in Figure 8b, binding is achieved through interactions between a pair of helices. Comparatively, the complex in Figure 8c contains a more extensive interface. In all these three cases, the native-like binding modes exist in the structural ensemble we constructed through the interface fragment pair library. In contrast, Figure 8d shows an example in which we failed to assemble the proteins into a complex that is close to the native quaternary structure. The interface of the receptor in this complex contains a long region of disordered loop. The corresponding fragment pairs in this interface may not appear in our library, leading into the result that its native-like binding cannot be derived.Figure 8

Bottom Line: After structural-based clustering, we found that more than 90% of these interface fragment pairs can be represented by a limited number of highly abundant motifs.Our study therefore presents supportive evidences that the space of protein quaternary structures can be represented by the combination of a small set of secondary-structure-based packing at binding interfaces.Finally, after future improvements such as adding sequence profiles, we expect this new library will be useful to predict structures of unknown protein-protein interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. Zhong-Ru.Xie@einstein.yu.edu.

ABSTRACT

Background: The physical interactions between proteins constitute the basis of protein quaternary structures. They dominate many biological processes in living cells. Deciphering the structural features of interacting proteins is essential to understand their cellular functions. Similar to the space of protein tertiary structures in which discrete patterns are clearly observed on fold or sub-fold motif levels, it has been found that the space of protein quaternary structures is highly degenerate due to the packing of compact secondary structure elements at interfaces. Therefore, it is necessary to further decompose the protein quaternary structural space into a more local representation.

Results: Here we constructed an interface fragment pair library from the current structure database of protein complexes. After structural-based clustering, we found that more than 90% of these interface fragment pairs can be represented by a limited number of highly abundant motifs. These motifs were further used to guide complex assembly. A large-scale benchmark test shows that the native-like binding is highly likely in the structural ensemble of modeled protein complexes that were built through the library.

Conclusions: Our study therefore presents supportive evidences that the space of protein quaternary structures can be represented by the combination of a small set of secondary-structure-based packing at binding interfaces. Finally, after future improvements such as adding sequence profiles, we expect this new library will be useful to predict structures of unknown protein-protein interactions.

Show MeSH
Related in: MedlinePlus