Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jan;17(1):72-8.
doi: 10.1110/ps.073196308.

Identification of transient hub proteins and the possible structural basis for their multiple interactions

Miho Higurashi  1 , Takashi Ishida, Kengo Kinoshita
Affiliations

Identification of transient hub proteins and the possible structural basis for their multiple interactions

Miho Higurashi et al. Protein Sci. 2008 Jan.

Abstract

Proteins that can interact with multiple partners play central roles in the network of protein-protein interactions. They are called hub proteins, and recently it was suggested that an abundance of intrinsically disordered regions on their surfaces facilitates their binding to multiple partners. However, in those studies, the hub proteins were identified as proteins with multiple partners, regardless of whether the interactions were transient or permanent. As a result, a certain number of hub proteins are subunits of stable multi-subunit proteins, such as supramolecules. It is well known that stable complexes and transient complexes have different structural features, and thus the statistics based on the current definition of hub proteins will hide the true nature of hub proteins. Therefore, in this paper, we first describe a new approach to identify proteins with multiple partners dynamically, using the Protein Data Bank, and then we performed statistical analyses of the structural features of these proteins. We refer to the proteins as transient hub proteins or sociable proteins, to clarify the difference with hub proteins. As a result, we found that the main difference between sociable and nonsociable proteins is not the abundance of disordered regions, in contrast to the previous studies, but rather the structural flexibility of the entire protein. We also found greater predominance of charged and polar residues in sociable proteins than previously reported.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Examples of sociable proteins. (A) Ran protein: It was found to interact with Ran binding protein (PDB: 1rrp), Ran GAP (PDB: 1k5d), karyopherin β2 (PDB: 1qbk), and nuclear transport factor 2 (PDB: 1a2k), and forms a dimer (PDB: 1byu). In addition, Ran can exist as a monomer (PDB: 1qg4). (B) α-Actin 1 (PDB: 2fxu): It was found to interact with gelsolin segment 1 (PDB: 1p8z), deoxyribonuclease 1 (PDB: 2a40), profilin (PDB: 1hlu), vitamin D binding proteins (PDB: 1ma9), deoxyribonuclease and Wiskott-Aldrich syndrome protein interacting protein (PDB: 2a41), gelsolin and α-actin 1 (PDB: 1mdu), and α-actin 1 forms a dimer (PDB: 1yxq). In addition, α-actin 1 can exist as a monomer (PDB: 1s22).
Figure 2.
Figure 2.
Percentage of predicted disordered residues. The percentages of disordered residues in the interfaces and the whole surfaces of sociable proteins (black bars), nonsociable proteins (gray bars), and stable hub proteins (white bars), respectively. Error bars indicate the 95% confidence intervals of the mean values.
Figure 3.
Figure 3.
Comparison of structural flexibility between sociable and nonsociable proteins. For sociable (black bars), nonsociable (gray bars), and stable hub proteins (white bars), the distribution of maxRMSD (A) and the distribution of secondary structure composition in the interfaces (B) are shown, respectively. Error bars indicate the 95% confidence intervals of the mean values.
Figure 4.
Figure 4.
Comparison of sequence propensity between sociable and nonsociable proteins. (A) Percent differences in amino acid propensities are shown. Amino acid names are shown in one-letter codes at the bottom. (B) Mean hydropathy values are shown for sociable (black bar), nonsociable (gray bar), and stable hub proteins (white bar), respectively. Error bars indicate the 95% confidence intervals of the mean values. (C) Observed frequency ratios of atom contacts in sociable and nonsociable proteins in the natural logarithmic scale.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E. The Protein Data Bank. Nucleic Acids Res. 2000;28:235–242. - PMC - PubMed
    1. Bracken, C., Iakoucheva, L.M., Romero, P.R., Dunker, A.K. Combining prediction, computation and experiment for the characterization of protein disorder. Curr. Opin. Struct. Biol. 2004;14:570–576. - PubMed
    1. Dunker, A.K., Cortese, M.S., Romero, P., Iakoucheva, L.M., Uversky, V.N. Flexible nets—The roles of intrinsic disorder in protein interaction networks. FEBS J. 2005;272:5129–5148. - PubMed
    1. Dyson, H.J., Wright, P.E. Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 2005;6:197–208. - PubMed
    1. Eisenhaber, F., Argos, P. Improved strategy in analytic surface calculation for molecular systems: Handling of singularities and computational efficiency. J. Comput. Chem. 1993;14:1272–1280.

Publication types