| 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 PubMed
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 kon and 3300-fold lower Kd compared 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.
The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.,Shen Q, Zeng D, Zhao B, Bhatt VS, Li P, Cho JH ACS Chem Biol. 2017 May 19;12(5):1199-1203. doi: 10.1021/acschembio.7b00168. Epub, 2017 Apr 5. PMID:28368102[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Matsuda M, Tanaka S, Nagata S, Kojima A, Kurata T, Shibuya M. Two species of human CRK cDNA encode proteins with distinct biological activities. Mol Cell Biol. 1992 Aug;12(8):3482-9. PMID:1630456
- ↑ Lawrenson ID, Wimmer-Kleikamp SH, Lock P, Schoenwaelder SM, Down M, Boyd AW, Alewood PF, Lackmann M. Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 2002 Mar 1;115(Pt 5):1059-72. PMID:11870224
- ↑ Kobashigawa Y, Sakai M, Naito M, Yokochi M, Kumeta H, Makino Y, Ogura K, Tanaka S, Inagaki F. Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK. Nat Struct Mol Biol. 2007 Jun;14(6):503-10. Epub 2007 May 21. PMID:17515907 doi:10.1038/nsmb1241
- ↑ Shen Q, Zeng D, Zhao B, Bhatt VS, Li P, Cho JH. The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus. ACS Chem Biol. 2017 May 19;12(5):1199-1203. doi: 10.1021/acschembio.7b00168. Epub, 2017 Apr 5. PMID:28368102 doi:http://dx.doi.org/10.1021/acschembio.7b00168
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