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.

The vast accumulation of protein structural data has now facilitated the observation of many different complexes in the PDB for the same protein. Therefore, a single protein complex is not sufficient to identify their interaction sites, especially for proteins with multiple binding states or different partners, such as hub proteins. PiSite is a database that provides protein–protein interaction sites at the residue level with consideration of multiple complexes at the same time, by mapping the binding sites of all complexes containing the same protein in the PDB. PiSite provides easy web interfaces with an interactive viewer working with typical web browsers, and the different binding modes can be checked visually. All of the information can also be downloaded for further analyses. In addition, PiSite provides a list of proteins with multiple binding partners and multiple binding states, as well as up-to-date statistics of protein–protein interfaces. PiSite is available at http://pisite.hgc.jp

The (6-4) photoproduct formed by ultraviolet light is known as an alkali-labile DNA lesion. Strand breaks occur at (6-4) photoproducts when UV-irradiated DNA is treated with hot alkali. We have analyzed the degradation reaction of this photoproduct under alkaline conditions using synthetic oligonucleotides. A tetramer, d(GT(6-4)TC), was prepared, and its degradation in 50 mM KOH at 60°C was monitored by high performance liquid chromatography. A single peak with a UV absorption spectrum similar to that of the starting material was detected after the reaction, and this compound was UV light in solar radiation is absorbed by nucleobases in DNA and induces photochemical reactions. The major forms of DNA damage by UV radiation are the cis-syn cyclobutane pyrimidine dimer (CPD) 1 and the pyrimidine(6-4)pyrimidone photoproduct ((6-4) photoproduct) formed between adjacent pyrimidine bases (1). The formation of these lesions not only induces mutations of genetic information (2) but also alters the chemical stability of DNA. In the case of the CPD formed at the sequences containing cytosine, the hydrolysis rate of the amino function is much higher than that of the normal cytosine base (3), which results in the C3 T transition (4 -6). The (6-4) photoproduct was originally identified as a UV-induced alkalisensitive lesion (7,8). Strand breaks occur at the sites of this photoproduct when UV-irradiated DNA is treated with hot alkali, and this procedure has been used to map the (6-4) photoproduct in defined DNA sequences at nucleotide resolution (9 -12). This alkali lability has also been applied for footprinting experiments to analyze protein-DNA interactions in vivo (13,14). While the reactions of other alkali-labile DNA damages such as the apurinic/apyrimidinic (AP) site (15) and the bleomycin-induced lesion (16) have been analyzed in detail, the mechanism of the strand break caused at the (6-4) photoproduct by the alkali treatment has not been elucidated so far. Franklin et al. (8) suggested the hydrolysis of the glycosyl bond of the 3Ј component of this photoproduct, but there have been no subsequent reports.The (6-4) photoproduct is reportedly more mutagenic than the CPD (17-19) and blocks replication without being bypassed by error-free translesion synthesis, whereas DNA polymerase correctly incorporates dATP opposite the CPD formed at the TT sequence (20, 21). To avoid mutagenesis and carcinogenesis by the (6-4) photoproduct, this damage must be removed by the nucleotide excision repair (NER) pathway in cells (22)(23)(24). No base excision repair (BER) enzyme is known for the (6-4) photoproduct, but if the photoproduct can be degraded artificially, this DNA may be repaired by the BER pathway, even in xeroderma pigmentosum patients lacking NER function. For such an application, it is important to characterize the chemical properties of the (6-4) photoproduct.In this paper we describe the analysis of the alkali degradation of DNA containing the (6-4) photoproduct using chemically synthesized oligonucleotides. A relati...

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