Molecular sled sequences are common in mammalian proteins

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• A new class of molecular machines, termed molecular sleds, has been identified.
• These sleds are small molecules capable of binding and sliding along DNA, with potential for cargo transport.

Purpose of the Study:

• To investigate the fundamental mechanisms underlying the DNA sliding activity of molecular sleds.
• To identify the key components and functional motifs responsible for this activity.

Main Methods:

• Biochemical assays were employed to analyze molecular sled function.
• Single-molecule flow stretching assays were utilized to observe DNA binding and sliding dynamics.

Main Results:

• The functional core of pVIc, a known molecular sled, was identified.
• Specific peptide functional groups controlling DNA sliding activity were characterized.
• A model for the sliding mechanism of molecular sleds was proposed.
• Widespread DNA binding and sliding activity were observed in basic polypeptide sequences, including mammalian nuclear localization sequences and cell penetrating peptides.
• These motifs demonstrate physiologically relevant, sequence-nonspecific DNA affinity.

Conclusions:

• Many mammalian proteins likely possess molecular sled capabilities due to common basic polypeptide motifs.
• Undiscovered DNA sliding activities may be prevalent among nuclear mammalian proteins.
• This research expands our understanding of molecular machines interacting with DNA.