title: The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.
abstract: The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster konand 3300-fold lower Kdcompared to those for the CrkII-JNK1 interaction. These results provide molecular insight into the mechanism by which 1918 IAV NS1 hijacks CrkII and disrupts its interactions with critical cellular signaling proteins.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Danyun
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Baoyu
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Veer S
authors.initials: VS
authors.lastname: Bhatt
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Pingwei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Jae-Hyun
authors.identifier: 0000-0002-6190-6151
authors.initials: JH
authors.lastname: Cho
mesh_terms: D001665:Binding Sites; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry* / Q000472:pathogenicity; D064149:Influenza Pandemic, 1918-1919; D011485:Protein Binding; D050737:Proto-Oncogene Proteins c-crk / Q000737:chemistry / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: C085820:INS1 protein, influenza virus; D050737:Proto-Oncogene Proteins c-crk; D017361:Viral Nonstructural Proteins