Multidomain assembled states of Hck tyrosine kinase in solution

Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15757-62. doi: 10.1073/pnas.1004569107. Epub 2010 Aug 23.

Abstract

An approach combining small-angle X-ray solution scattering (SAXS) data with coarse-grained (CG) simulations is developed to characterize the assembly states of Hck, a member of the Src-family kinases, under various conditions in solution. First, a basis set comprising a small number of assembly states is generated from extensive CG simulations. Second, a theoretical SAXS profile for each state in the basis set is computed by using the Fast-SAXS method. Finally, the relative population of the different assembly states is determined via a Bayesian-based Monte Carlo procedure seeking to optimize the theoretical scattering profiles against experimental SAXS data. The study establishes the concept of basis-set supported SAXS (BSS-SAXS) reconstruction combining computational and experimental techniques. Here, BSS-SAXS reconstruction is used to reveal the structural organization of Hck in solution and the different shifts in the equilibrium population of assembly states upon the binding of different signaling peptides.

Publication types

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

MeSH terms

  • Bayes Theorem
  • Humans
  • Models, Molecular
  • Monte Carlo Method
  • Protein Conformation
  • Proto-Oncogene Proteins c-hck / chemistry*
  • Scattering, Radiation
  • Solutions

Substances

  • Solutions
  • HCK protein, human
  • Proto-Oncogene Proteins c-hck