Keywords
Last Name

Assen G. Marintchev, PhD

TitleAssistant Professor
InstitutionBoston University School of Medicine
DepartmentPhysiology & Biophysics
Address72 E. Concord St Instructional (L)
Boston MA 02118
Phone(617) 638-4295
ORCID ORCID Icon0000-0002-9901-3500
 Research Expertise & Professional Interests
Molecular Mechanisms of Eukaryotic Translation Initiation and its Regulation:

Control of protein synthesis (translation) is vital for cell proliferation and differentiation. Initiation of translation is typically rate-limiting and is the main target of regulation. In cancer cells, multiple components of the translation initiation machinery are up-regulated in response to the demand for high rates of protein synthesis. The potential of using inhibitors of translation initiation for anti-cancer therapy was demonstrated in recent years and currently presents an active area of research.

Translation initiation is the process of locating the correct translation start codon on the mRNA and the assembly of an active ribosome, ready for translation. It requires a number of eukaryotic translation initiation factors (eIFs) and consists of several steps: initiation complex assembly; binding to mRNA; scanning; start codon recognition; and finally joining of the large ribosomal subunit to form a ribosome with a bound initiator Met-tRNAi ready to translate the mRNA. The initiator Met-tRNAi is delivered to the ribosome as a complex with eIF2-GTP. One eIF2-GTP:Met-tRNAi complex is “consumed” in every translation initiation cycle, with release of eIF2-GDP and deacylated initiator tRNAi. Regeneration of the eIF2-GTP:Met-tRNAi complex from eIF2-GDP and Met-tRNAi is catalyzed by the nucleotide exchange factor (GEF) eIF2B (reviewed in Marintchev and Wagner, 2004).

Our work is focused on studying the architecture of the translation initiation complexes, the molecular mechanisms of key steps in the process, and their regulation. The long-term goal is to build a detailed mechanistic and quantitative model of translation initiation as a whole, and learn how to rationally manipulate the system for the purposes of cancer therapy and treatment of metabolic disorders. Two areas of particular interest are the coordination between start codon selection and ribosomal subunit joining, and the regeneration of the eIF2-GTP:Met-tRNAi complex.

 Self-Described Keywords
  • Bioinformatics
  • Fluorescence anisotropy
  • FRET
  • NMR
  • Protein structure
  • Translation
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Bogorad AM, Xia B, Sandor DG, Mamonov AB, Cafarella TR, Jehle S, Vajda S, Kozakov D, Marintchev A. Insights into the Architecture of the eIF2Ba/ß/d Regulatory Subcomplex. Biochemistry. 2014 Jun 3; 53(21):3432-45.
    View in: PubMed
  2. Marintchev A. Roles of helicases in translation initiation: a mechanistic view. Biochim Biophys Acta. 2013 Aug; 1829(8):799-809.
    View in: PubMed
  3. Marintchev, A. In: Dinman, J.D. (Ed.) Biophysical approaches to translational control of gene expression. Methods for studying the interactions of translation factors with the ribosome. Springer. New York, NY. 2013; 1:pp 83-101.
    View in: External Website
  4. Luna RE, Arthanari H, Hiraishi H, Nanda J, Martin-Marcos P, Markus MA, Akabayov B, Milbradt AG, Luna LE, Seo HC, Hyberts SG, Fahmy A, Reibarkh M, Miles D, Hagner PR, O'Day EM, Yi T, Marintchev A, Hinnebusch AG, Lorsch JR, Asano K, Wagner G. The C-terminal domain of eukaryotic initiation factor 5 promotes start codon recognition by its dynamic interplay with eIF1 and eIF2ß. Cell Rep. 2012 Jun 28; 1(6):689-702.
    View in: PubMed
  5. Marintchev A. Fidelity and quality control in gene expression. Preface. Adv Protein Chem Struct Biol. 2012; 86:ix.
    View in: PubMed
  6. Yu Y, Abaeva IS, Marintchev A, Pestova TV, Hellen CU. Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors. Nucleic Acids Res. 2011 Jun; 39(11):4851-65.
    View in: PubMed
  7. Abaeva IS, Marintchev A, Pisareva VP, Hellen CU, Pestova TV. Bypassing of stems versus linear base-by-base inspection of mammalian mRNAs during ribosomal scanning. EMBO J. 2011 Jan 5; 30(1):115-29.
    View in: PubMed
  8. Yu Y, Marintchev A, Kolupaeva VG, Unbehaun A, Veryasova T, Lai SC, Hong P, Wagner G, Hellen CU, Pestova TV. Position of eukaryotic translation initiation factor eIF1A on the 40S ribosomal subunit mapped by directed hydroxyl radical probing. Nucleic Acids Res. 2009 Aug; 37(15):5167-82.
    View in: PubMed
  9. Marintchev A, Edmonds KA, Marintcheva B, Hendrickson E, Oberer M, Suzuki C, Herdy B, Sonenberg N, Wagner G. Topology and regulation of the human eIF4A/4G/4H helicase complex in translation initiation. Cell. 2009 Feb 6; 136(3):447-60.
    View in: PubMed
  10. Suzuki C, Garces RG, Edmonds KA, Hiller S, Hyberts SG, Marintchev A, Wagner G. PDCD4 inhibits translation initiation by binding to eIF4A using both its MA3 domains. Proc Natl Acad Sci U S A. 2008 Mar 4; 105(9):3274-9.
    View in: PubMed
  11. Lindqvist L, Oberer M, Reibarkh M, Cencic R, Bordeleau ME, Vogt E, Marintchev A, Tanaka J, Fagotto F, Altmann M, Wagner G, Pelletier J. Selective pharmacological targeting of a DEAD box RNA helicase. PLoS One. 2008; 3(2):e1583.
    View in: PubMed
  12. Marintcheva B, Marintchev A, Wagner G, Richardson CC. Acidic C-terminal tail of the ssDNA-binding protein of bacteriophage T7 and ssDNA compete for the same binding surface. Proc Natl Acad Sci U S A. 2008 Feb 12; 105(6):1855-60.
    View in: PubMed
  13. Unbehaun A, Marintchev A, Lomakin IB, Didenko T, Wagner G, Hellen CU, Pestova TV. Position of eukaryotic initiation factor eIF5B on the 80S ribosome mapped by directed hydroxyl radical probing. EMBO J. 2007 Jul 11; 26(13):3109-23.
    View in: PubMed
  14. Marintchev A, Frueh D, Wagner G. NMR methods for studying protein-protein interactions involved in translation initiation. Methods Enzymol. 2007; 430:283-331.
    View in: PubMed
  15. Gelev V, Aktas H, Marintchev A, Ito T, Frueh D, Hemond M, Rovnyak D, Debus M, Hyberts S, Usheva A, Halperin J, Wagner G. Mapping of the auto-inhibitory interactions of protein kinase R by nuclear magnetic resonance. J Mol Biol. 2006 Dec 1; 364(3):352-63.
    View in: PubMed
  16. Yamamoto Y, Singh CR, Marintchev A, Hall NS, Hannig EM, Wagner G, Asano K. The eukaryotic initiation factor (eIF) 5 HEAT domain mediates multifactor assembly and scanning with distinct interfaces to eIF1, eIF2, eIF3, and eIF4G. Proc Natl Acad Sci U S A. 2005 Nov 8; 102(45):16164-9.
    View in: PubMed
  17. Marintchev A, Wagner G. eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G. Biochemistry. 2005 Sep 20; 44(37):12265-72.
    View in: PubMed
  18. Oberer M, Marintchev A, Wagner G. Structural basis for the enhancement of eIF4A helicase activity by eIF4G. Genes Dev. 2005 Sep 15; 19(18):2212-23.
    View in: PubMed
  19. Ito T, Marintchev A, Wagner G. Solution structure of human initiation factor eIF2alpha reveals homology to the elongation factor eEF1B. Structure. 2004 Sep; 12(9):1693-704.
    View in: PubMed
  20. Marintchev A, Wagner G. Translation initiation: structures, mechanisms and evolution. Q Rev Biophys. 2004 Aug-Nov; 37(3-4):197-284.
    View in: PubMed
  21. Lomakin IB, Kolupaeva VG, Marintchev A, Wagner G, Pestova TV. Position of eukaryotic initiation factor eIF1 on the 40S ribosomal subunit determined by directed hydroxyl radical probing. Genes Dev. 2003 Nov 15; 17(22):2786-97.
    View in: PubMed
  22. Marintchev A, Kolupaeva VG, Pestova TV, Wagner G. Mapping the binding interface between human eukaryotic initiation factors 1A and 5B: a new interaction between old partners. Proc Natl Acad Sci U S A. 2003 Feb 18; 100(4):1535-40.
    View in: PubMed
  23. Marintchev A, Gryk MR, Mullen GP. Site-directed mutagenesis analysis of the structural interaction of the single-strand-break repair protein, X-ray cross-complementing group 1, with DNA polymerase beta. Nucleic Acids Res. 2003 Jan 15; 31(2):580-8.
    View in: PubMed
  24. Gryk MR, Marintchev A, Maciejewski MW, Robertson A, Wilson SH, Mullen GP. Mapping of the interaction interface of DNA polymerase beta with XRCC1. Structure. 2002 Dec; 10(12):1709-20.
    View in: PubMed
  25. Maciejewski MW, Shin R, Pan B, Marintchev A, Denninger A, Mullen MA, Chen K, Gryk MR, Mullen GP. Solution structure of a viral DNA repair polymerase. Nat Struct Biol. 2001 Nov; 8(11):936-41.
    View in: PubMed
  26. Pan B, Maciejewski MW, Marintchev A, Mullen GP. Solution structure of the catalytic domain of gammadelta resolvase. Implications for the mechanism of catalysis. J Mol Biol. 2001 Jul 27; 310(5):1089-107.
    View in: PubMed
  27. Wu H, Maciejewski MW, Marintchev A, Benashski SE, Mullen GP, King SM. Solution structure of a dynein motor domain associated light chain. Nat Struct Biol. 2000 Jul; 7(7):575-9.
    View in: PubMed
  28. Marintchev A, Robertson A, Dimitriadis EK, Prasad R, Wilson SH, Mullen GP. Domain specific interaction in the XRCC1-DNA polymerase beta complex. Nucleic Acids Res. 2000 May 15; 28(10):2049-59.
    View in: PubMed
  29. Marintchev A, Mullen MA, Maciejewski MW, Pan B, Gryk MR, Mullen GP. Solution structure of the single-strand break repair protein XRCC1 N-terminal domain. Nat Struct Biol. 1999 Sep; 6(9):884-93.
    View in: PubMed
  30. Marintchev A, Maciejewski MW, Mullen GP. 1H, 15N, and 13C resonance assignments for the N-terminal 20 kDa domain of the DNA single-strand break repair protein XRCC1. J Biomol NMR. 1999 Apr; 13(4):393-4.
    View in: PubMed
  31. Marintchev A, Mirtcheva J, Sidjimov A, Haimova M. Induction of lymphoproliferative popliteal lymph node reaction by hydantoin derivatives: structure-activity relationships. Int J Immunopharmacol. 1995 Dec; 17(12):981-4.
    View in: PubMed
Assen's Networks
Click the "See All" links for more information and interactive visualizations!
Concepts
_
BU Co-Authors
_
Similar BU People
_
Same Department