4QT7

Crystal structure of the c-Src SH3 domain in complex with a peptide from the Hepatitis C virus NS5A-protein

Summary for 4QT7

• Entry DOI: 10.2210/pdb4qt7/pdb
• Descriptor: Proto-oncogene tyrosine-protein kinase Src, NS5A (3 entities in total)
• Functional Keywords: beta shandwich, sh3 domain, proline rich motifs, viral protein, transferase-transferase activator complex, transferase/transferase activator
• Biological source: Gallus gallus (bantam,chickens); More
• Cellular location: Cell membrane : P00523
• Total number of polymer chains: 2
• Total formula weight: 8220.12

Authors

Camara-Artigas, A.,Bacarizo, J. (deposition date: 2014-07-07, release date: 2014-12-24, Last modification date: 2024-11-13)

Primary citation

Bacarizo, J.,Martinez-Rodriguez, S.,Camara-Artigas, A.
Structure of the c-Src-SH3 domain in complex with a proline-rich motif of NS5A protein from the hepatitis C virus.
J.Struct.Biol., 189:67-72, 2015

PubMed Abstract: The non-structural hepatitis C virus proteins NS5A and NS5B form a complex through interaction with the SH2 and SH3 domains of the non-receptor Src tyrosine kinase, which seems essential for viral replication. We have crystallized the complex between the SH3 domain of the c-Src tyrosine kinase and the C-terminal proline rich motif of the NS5A protein (A349PPIPPPRRKR359). Crystals obtained at neutral pH belong to the space group I41, with a single molecule of the SH3/NS5A complex at the asymmetric unit. The NS5A peptide is bound in a reverse orientation (class II) and the comparison of this structure with those of the high affinity synthetic peptides APP12 and VSL12 shows some important differences at the salt bridge that drives the peptide orientation. Further conformational changes in residues placed apart from the binding site also seem to play an important role in the binding orientation of this peptide. Our results show the interaction of the SH3 domain of the c-Src tyrosine kinase with a proline rich motif in the NS5A protein and point to their potential interaction in vivo.

PubMed: 25447263
DOI: 10.1016/j.jsb.2014.11.004

Experimental method

X-RAY DIFFRACTION (1.55 Å)