Small heat shock proteins (sHSPs) are oligomeric stress proteins characterized by an -crystallin domain (ACD) surrounded by a N-terminal arm and C-terminal extension. as well as recycling photosynthetically fixed organic carbon as dissolved organic material via viral lysis . Cyanophages infect the marine unicellular cyanobacteria, 239101-33-8 IC50 and its sister group which dominate the picophytoplankton in the oceans [13,14]. To date, the vast majority of phages that are known to infect cyanobacteria are myoviruses [15,16], which are related to phage T4 [17,18]. It has been reported that the sequenced genomes of and phages contain genes with an hsp20/alpha-crystallin domain (PF00011) [18-20]. Materials hJumpy and Methods Sequence databases, alignment and phylogeny We searched the presence of sHSPs in the complete sequenced genomes of viruses 239101-33-8 IC50 from the biological databases (GenBank, protein database, and genomes database) using BLASTp, tBLASTn and HMM profile. We have also searched sHSPs in complete sequenced genomes of their host cyanobacteria, and phage sHSP S-MbCM6 (HspSP-MbCM6) and sp. PCC 7335.1 sHSP (HspS-PCC7335.1) were constructed using I-TASSER which combines the methods of threading, modeling and structural refinement . Structures of Hsp16.0 from (PDB: 3w1z), Hsp16.9 from (PDB: 1gme) and B-crystallin from human (2ygd) were used as templates for HspSP-MbCM6. 3w1z, 1gme and Hsp16.5 from (PDB: 4eld) served as template for HspS-PCC7335.1. Search of structure similiraty of obtained 3D models was conducted by PDBeFold  against PDB database. The electrostatic potential surface of sHSP 3D models was realized with PyMOL software (http://pymol.org/). Pairwise 3D models alignment was performed using Matras software . Docking of the C-terminal extension of cyanophage (HspSP-MbCM6) and cyanobacteria (HspS-PCC7335.1) into hydrophobic pockets of ?4/?8 strands region revealed by electrostatic potential surface analysis, was conducted by structure alignment to tetramer of wheat Hsp16.9 (PDB: 1gme). Results and Discussion Publications on sHSPs have reported that they are present in archaea, bacteria, fungi, plants and animals but not in viruses. Here, we searched for sHSPs in the complete sequenced genomes of viruses from the biological databases (GenBank, protein database, and genomes database) using BLASTp, tBLASTn and HMM profile. These searches showed that sHSPs are present only in marine viruses (cyanophages) that infect the unicellular cyanobacteria, and (Table 1). We found that the genomes of many, but not all, of these cyanophages contain a single-copy sHSPs gene. Small cyanophage genomes such as phage P60 (47872 bp) and phage Syn5 (46214 bp) do not contain any sHSP genes. It is interesting to note that phage P-SSM2 and P-SSM4 lack core T4-like chaperonin genes (rnlA, 31, and 57A), although, both phages contain sHSPs . sHSPs could play the same function as core T4-like chaperonin genes intervening in scaffolding during maturation of the capsid . Protein sequence analysis of cyanophage sHSPs showed that they contain a conserved ACD (~ 92 amino acids) flanked by a relatively conserved N-terminal arm and a short C-terminal extension. The length of the arm and the extension is variable. Conserved C-terminal anchoring motif (CAM) L-X-I/L/V, implicated in the inter-dimer interactions is present in 12 of 19 phages (Figure 1). The phages do not contain a classical CAM but A-X-P, L-X-G and L-X-A motives are present in the C-terminal extension of phages Syn33, P-SSM2 and P-SSM7, respectively. It was reported that sHSP Tsp36 also contains a non-classical CAM, I-X-P . The end of N-terminal arm contains a double conserved proline and another conserved proline is 239101-33-8 IC50 present at the beginning of the C-terminal extension (Figure 1). Furthermore, an A-G doublet characteristic of bacterial class A sHSPs is also present in cyanophage sHSPs [29,30] . This doublet is sandwiched by hydrophobic residues, aliphatic residue L and aromatic F/Y/W. Aromatic residues in this position are found only in bacterial classA and animals sHSPs . Cyanophages also have a conserved arginine, important for dimerization and associated with human diseases in the predicted 7 strand (Figure 1). phage S-PM2, S-CAM1 and Prochlorococcus phage Syn1 contain a hydrophilic amino acid asparagine in the place of arginine, and phage S-CRM01 contains a lysine. The ACD contains a variable region corresponding to the L57 loop (residues 109-121) (Figure 1). Arg in beta7 strand could form salt bridge with Asp or Glu in the L57 loop (residues 109-121) of the neighbor monomer, probably with Asp or Glu in position 117 (Figure 1). Using I-TASSER, we have constructed a 3D model of the sHSP from phage S-MbCM6 (HspSP-MbCM6). Figure 2A shows that 3D model is similar to the structure of wheat Hsp16.9 . 3D structure alignment between HspSP-MbCM6 and wheat Hsp16.9 (Figure 2B) showed that the best conserved region is the ACD domain. 3D alignment by PDBeFold of the 3D model against PDB database revealed a.