Addressing the Binding Mechanism of the Meprin and TRAF-C Homology Domain of the Speckle-Type POZ Protein Using Protein Engineering

被引:1
|
作者
Diop, Awa [1 ]
Pietrangeli, Paola [1 ]
Pennacchietti, Valeria [1 ]
Pagano, Livia [1 ]
Toto, Angelo [1 ]
Di Felice, Mariana [1 ]
Di Matteo, Sara [1 ]
Marcocci, Lucia [1 ]
Malagrino, Francesca [2 ]
Gianni, Stefano [1 ]
机构
[1] Sapienza Univ Roma, Fdn Cenci Bolognetti, Lab Affiliated Ist Pasteur Italia, Dipartimento Sci Biochim A Rossi Fanelli, Piazzale Aldo Moro 5, I-00185 Rome, Italy
[2] Univ Aquila, Dept Life Hlth & Environm Sci, I-67100 Coppito, Italy
关键词
kinetics; protein-protein interactions; MATH domain; speckle-type POZ protein; site-directed mutagenesis; TRANSITION-STATE; UBIQUITIN; SPOP; INSIGHTS; ORDER;
D O I
10.3390/ijms242417364
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein-protein interactions play crucial roles in a wide range of biological processes, including metabolic pathways, cell cycle progression, signal transduction, and the proteasomal system. For PPIs to fulfill their biological functions, they require the specific recognition of a multitude of interacting partners. In many cases, however, protein-protein interaction domains are capable of binding different partners in the intracellular environment, but they require precise regulation of the binding events in order to exert their function properly and avoid misregulation of important molecular pathways. In this work, we focused on the MATH domain of the E3 Ligase adaptor protein SPOP in order to decipher the molecular features underlying its interaction with two different peptides that mimic its physiological partners: Puc and MacroH2A. By employing stopped-flow kinetic binding experiments, together with extensive site-directed mutagenesis, we addressed the roles of specific residues, some of which, although far from the binding site, govern these transient interactions. Our findings are compatible with a scenario in which the binding of the MATH domain with its substrate is characterized by a fine energetic network that regulates its interactions with different ligands. Results are briefly discussed in the context of previously existing work regarding the MATH domain.
引用
收藏
页数:12
相关论文
共 50 条
  • [31] RNA interference-mediated silencing of speckle-type POZ protein promotes apoptosis of renal cell cancer cells
    Liu, Xiaoxia
    Sun, Guiling
    Sun, Xiuju
    ONCOTARGETS AND THERAPY, 2016, 9 : 2393 - 2402
  • [32] BTB domain-containing speckle-type POZ protein (SPOP) serves as an adaptor of Daxx for ubiquitination by Cul3-based ubiquitin ligase
    Kwon, JE
    La, M
    Oh, KH
    Oh, YM
    Kim, GR
    Seol, JH
    Baek, SH
    Chiba, T
    Tanaka, K
    Bang, OS
    Joe, CO
    Chung, CH
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (18) : 12664 - 12672
  • [33] Computational approach for predicting the functional effects of missense variants on Speckle-type BTB/POZ protein and association with prostate cancer
    Berjas Abumsimir
    Yassine Kasmi
    Moulay Mustapha Ennaji
    Journal of Proteins and Proteomics, 2020, 11 (3) : 205 - 212
  • [34] SPECKLE-TYPE POZ PROTEIN CYTOPLASMIC MISLOCALIZATION AND OVEREXPRESSION PROMOTE TUMOR GROWTH IN AN ORTHOTOPIC MURINE RENAL CELL CANCER MODEL
    Prasad, Sandip
    Karmakar, Subhradip
    Cai, Yi
    VanderGriend, Donald
    White, Kevin
    Eggener, Scott
    JOURNAL OF UROLOGY, 2012, 187 (04): : E60 - E60
  • [35] Loss of Speckle-Type POZ Protein Promotes Prostate Cancer Cell Migration and Invasion Through Upregulation of MCP-1
    Shi, Junlin
    Cao, Ji
    Lu, Xiaomei
    Fan, Langlin
    Guo, Hongwei
    Fu, Jiejun
    MEDICAL SCIENCE MONITOR, 2021, 27
  • [36] Immunohistochemical Analysis of Speckle-Type POZ Protein (SPOP) in Prostate Cancer, High Grade Prostatic Intraepithelial Neoplasia and Benign Glands
    Razmaria, A.
    Cohn, J.
    White, K.
    VanderGriend, D.
    Paner, G. P.
    LABORATORY INVESTIGATION, 2013, 93 : 243A - 243A
  • [37] Immunohistochemical Analysis of Speckle-Type POZ Protein (SPOP) in Prostate Cancer, High Grade Prostatic Intraepithelial Neoplasia and Benign Glands
    Razmaria, A.
    Cohn, J.
    White, K.
    VanderGriend, D.
    Paner, G. P.
    MODERN PATHOLOGY, 2013, 26 : 243A - 243A
  • [38] Decreased expression of speckle-type POZ protein for the prediction of poor prognosis in patients with non-small cell lung cancer
    Li, Jing-Jing
    Zhang, Jian-Feng
    Yao, Su-Mei
    Huang, Hua
    Zhang, Shu
    Zhao, Minxing
    Huang, Jian-An
    ONCOLOGY LETTERS, 2017, 14 (03) : 2743 - 2748
  • [39] Speckle-type POZ (pox virus and zinc finger protein) protein gene deletion in ovarian cancer: Fluorescence in situ hybridization analysis of a tissue microarray
    Hu, Xiaoyu
    Yang, Zhu
    Zeng, Manman
    Liu, Yi
    Yang, Xiaotao
    Li, Yanan
    Li, Xu
    Yu, Qiubo
    ONCOLOGY LETTERS, 2016, 12 (01) : 658 - 662
  • [40] SPECKLE-TYPE POZ PROTEIN CYTOPLASMIC MISLOCALIZATION AND OVEREXPRESSION PROMOTE TUMOR GROWTH IN AN ORTHOTOPIC MURINE RENAL CELL CARCINOMA MODEL
    Golan, Shay
    Prasad, Sandip
    Famakinwa, Fenwa
    Cai, Yi
    Vandergriend, Donald
    Eggener, Scott E.
    White, Kevin P.
    JOURNAL OF ENDOUROLOGY, 2012, 26 : A15 - A16