title: Molecular sled sequences are common in mammalian proteins.
abstract: Recent work revealed a new class of molecular machines called molecular sleds, which are small basic molecules that bind and slide along DNA with the ability to carry cargo along DNA. Here, we performed biochemical and single-molecule flow stretching assays to investigate the basis of sliding activity in molecular sleds. In particular, we identified the functional core of pVIc, the first molecular sled characterized; peptide functional groups that control sliding activity; and propose a model for the sliding activity of molecular sleds. We also observed widespread DNA binding and sliding activity among basic polypeptide sequences that implicate mammalian nuclear localization sequences and many cell penetrating peptides as molecular sleds. These basic protein motifs exhibit weak but physiologically relevant sequence-nonspecific DNA affinity. Our findings indicate that many mammalian proteins contain molecular sled sequences and suggest the possibility that substantial undiscovered sliding activity exists among nuclear mammalian proteins.
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Department of Biological Engineering, MIT, Cambridge, MA 02142, USA.
authors: Kan
authors: K
authors: Xiong
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Department of Biological Engineering, MIT, Cambridge, MA 02142, USA pblainey@mit.edu.
authors: Paul C
authors: PC
authors: Blainey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D010582:Bacteriophage lambda / Q000737:chemistry; D001681:Biological Assay; D001710:Biotin / Q000737:chemistry; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D004271:DNA, Fungal / Q000737:chemistry*; D008322:Mammals; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D012212:Rheology; D055672:Static Electricity; D019809:Streptavidin / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D004271:DNA, Fungal; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014764:Viral Proteins; C105093:glycyl-valyl-glutaminyl-seryl-leucyl-lysyl-arginyl-arginyl-arginyl-cysteinyl-phenylalanine; D001710:Biotin; D019809:Streptavidin