6atv | pdb_00006atv
The molecular mechanisms by which NS1 of the 1918 Spanish influenza A virus hijack host protein-protein interactions
Structural highlights
Function[CRK_HUMAN] The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.[1] [2] [3] Publication Abstract from PubMedMany intrinsically disordered proteins (IDPs) form fuzzy complexes upon binding to their targets. Although many IDPs are weakly bound in fuzzy complexes, some IDPs form high-affinity complexes. One example is the nonstructural protein 1 (NS1) of the 1918 Spanish influenza A virus, which hijacks cellular CRKII through the strong binding affinity (Kd approximately 10 nM) of its proline-rich motif (PRM(NS1)) to the N-terminal Src-homology 3 domain of CRKII. However, its molecular mechanism remains elusive. Here, we examine the interplay between structural disorder of a bound PRM(NS1) and its long-range electrostatic interactions. Using x-ray crystallography and NMR spectroscopy, we found that PRM(NS1) retains substantial conformational flexibility in the bound state. Moreover, molecular dynamics simulations showed that structural disorder of the bound PRM(NS1) increases the number of electrostatic interactions and decreases the mean distances between the positively charged residues in PRM(NS1) and the acidic residues in the N-terminal Src-homology 3 domain. These results are analyzed using a polyelectrostatic model. Our results provide an insight into the molecular recognition mechanism for a high-affinity fuzzy complex. Molecular Mechanisms of Tight Binding through Fuzzy Interactions.,Shen Q, Shi J, Zeng D, Zhao B, Li P, Hwang W, Cho JH Biophys J. 2018 Mar 27;114(6):1313-1320. doi: 10.1016/j.bpj.2018.01.031. PMID:29590589[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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