The LC Domain of hnRNPA2 Adopts Similar Conformations in Hydrogel Polymers, Liquid-like Droplets, and Nuclei

Cell. 2015 Nov 5;163(4):829-39. doi: 10.1016/j.cell.2015.10.040.


Many DNA and RNA regulatory proteins contain polypeptide domains that are unstructured when analyzed in cell lysates. These domains are typified by an over-representation of a limited number of amino acids and have been termed prion-like, intrinsically disordered or low-complexity (LC) domains. When incubated at high concentration, certain of these LC domains polymerize into labile, amyloid-like fibers. Here, we report methods allowing the generation of a molecular footprint of the polymeric state of the LC domain of hnRNPA2. By deploying this footprinting technique to probe the structure of the native hnRNPA2 protein present in isolated nuclei, we offer evidence that its LC domain exists in a similar conformation as that described for recombinant polymers of the protein. These observations favor biologic utility to the polymerization of LC domains in the pathway of information transfer from gene to message to protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Nucleus / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / chemistry*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Humans
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Schistosoma japonicum / enzymology
  • Tyrosine / analysis


  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • Recombinant Proteins
  • hnRNP A2
  • Tyrosine