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Structure of the c-Src-SH3 domain in complex with a proline-rich motif of NS5A protein from the hepatitis C virus.

Bacarizo J, Martínez-Rodríguez S, Cámara-Artigas A
J Struct Biol 189 67-72 (2015)
Cited: 8 times
EuropePMC logo PMID: 25447263

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.

Articles - 4qt7 mentioned but not cited (3)

  1. Identification of two distinct peptide-binding pockets in the SH3 domain of human mixed-lineage kinase 3. Kokoszka ME, Kall SL, Khosla S, McGinnis JE, Lavie A, Kay BK. J Biol Chem 293 13553-13565 (2018)
  2. Molecular basis for the interaction between human choline kinase alpha and the SH3 domain of the c-Src tyrosine kinase. Kall SL, Whitlatch K, Smithgall TE, Lavie A. Sci Rep 9 17121 (2019)
  3. Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis. Mao J, Zhu K, Long Z, Zhang H, Xiao B, Xi W, Wang Y, Huang J, Liu J, Shi X, Jiang H, Lu T, Wen Y, Zhang N, Meng Q, Zhou H, Ruan Z, Wang J, Luo C, Xi X. Adv Sci (Weinh) 9 e2103228 (2022)


Reviews citing this publication (1)

  1. Crystallographic studies on protein misfolding: Domain swapping and amyloid formation in the SH3 domain. Cámara-Artigas A. Arch Biochem Biophys 602 116-126 (2016)

Articles citing this publication (4)

  1. Livin in synergy with Ras induces and sustains corticosteroid resistance in the airway mucosa. Xue JM, An YF, Suo LM, Mo LH, Yang G, Luo XQ, Liu DB, Zhao CQ, Yang PC. Int J Biol Sci 17 2089-2098 (2021)
  2. The impact of oncogenic mutations of the viral Src kinase on the structure and stability of the SH3 domain. Salinas-Garcia MC, Plaza-Garrido M, Camara-Artigas A. Acta Crystallogr D Struct Biol 77 854-866 (2021)
  3. ASPP2 binds to hepatitis C virus NS5A protein via an SH3 domain/PxxP motif-mediated interaction and potentiates infection. Smirnov A, Magri A, Lotz R, Han X, Yin C, Harris M, Osterburg C, Dötsch V, McKeating JA, Lu X. J Gen Virol 104 (2023)
  4. WW domains: A globular NLS recognized by importin-α. Bernardes NE, Chook YM. J Cell Biol 223 e202405003 (2024)


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