LAST motifs and SMART domains in gene 32 protein: an unfolding story of autoregulation?
Bacteriophage T4 gene 32 protein is a classical single strand-specific DNA binding protein. It is a single polypeptide chain of 301 amino acid residues that consists of three structural domains, each of which has a binding function. The N-terminal domain is involved in homotypic protein-protein interaction (the basis of binding cooperativity), the core domain binds single strands directly, and the C-terminal domain has a role in heterotypic protein-protein association. The three domains have traditionally been thought to be independent of each other. However, the observation of a striking repetition of a basic, polar sequence (the "LAST" Motif), seen in both the N-terminal and core domains, suggests a linkage between these domains. Moreover, the C-domain and adjoining portion (flap) of the core are highly acidic, and are potential mimics of single-stranded DNA. With these observations, I construct a model in which this flap is associated with the ssDNA binding site in the absence of DNA, and upon cooperative protein binding to DNA, the flap now associates with the N-terminal domain of the adjacent DNA-bound protein. The flap thus acts as a gate, which might slow the binding of the protein to DNA. This could lead to the regulation of the protein's various interactions with other proteins, as well as affect its ability to lower DNA melting temperature.
Karpel
Richard L
RL
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore 21250, USA. karpel@umbc.edu
D017122:Bacteriophage T4 / Q000235:genetics*; D001665:Binding Sites; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D008957:Models, Genetic; D008958:Models, Molecular; D011487:Protein Conformation; D014764:Viral Proteins / Q000235:genetics*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D014764:Viral Proteins; C060035:gp32 protein, Enterobacteria phage T4