University homepage Suomeksi På svenska In English
University of Helsinki Institute of Biotechnology
Institute of Biotechnology
Biomolecular NMR & Protein Engineering

Group Leader
Dr. Hideo Iwai
Tel: +358-9-191 59752
E-mail: hideo -dot- iwai
-at- helsinki -dot- fi

Institute of Biotechnology
Street address: Viikinkaari 1 (P.O.Box 65)
00014 University of Helsinki
Tel: +358-9-191 1
fax +358-9-1915 9541

Business Identity Code:
(University of Helsinki)

Telephone directory (all contact information included)

E-mail directory

How to get here
(Helsinki city map)

Research in Hideo Iwai's Laboratory

Our research goal is to understand how proteins exert their functions at atomic resolution in living organisms and to create new biotechnological and biomedical applications by protein engineering, based on biophysical and structural information of proteins.

Protein Splicing and related phenomena

 Our group is interested in biology, chemistry, and applications of protein-splicing discovered in 1990. Protein splicing is an autocatalytic post-translational modification, in which an intervening protein sequence catalyzes precise self-excision from the precursor protein and concomitantly ligates the flanking host sequence to produce a mature active host protein. Because of the analogy to intron and exon in RNA splicing, protein-splicing elements are called internal protein (intein) and external protein (extein). More than 500 inteins have been identified in all three kingdoms of life (eubacteria, archaea, and eukaryote) but not in multi-cellular organisms. Therefore, protein splicing could be a novel specific drug target of organisms containing protein-splicing elements such as Mycobacterium tuberculosis. Many of inteins also contain an endonuclease domain, which play a crucial role in spreading intein genes by horizontal gene transfer. Except for its endonuclease activity, no biological function has been discovered. Inteins also do not provide any clear benefit to host organisms. Therefore, intein has been considered as merely a parasitic gene element or selfish DNA. Intein’s origin, spread, and evolution still remain unclear. However, it has increasingly become very important biotechnological tools such as protein ligation and protein purification.

We are also investigating intein-related proteins (bacterial intein-like proteins and hedgehog proteins) for better understanding of evolutional origins of inteins. These proteins clearly share a part of protein-splicing mechanism. We are trying to understand:

1) Structure-Function Relationships of Inteins and related proteins.

2) Evolutional origins of inteins. (Horizontal transfer of intein genes)

3) Biological functions of inteins.

Alternative Splicing in Proteins

Segmental Isotopic Labeling for Protein NMR

Backbone Topology Engineering (Cyclic Peptides and Proteins)

 Protein drugs such as therapeutic antibodies are increasingly important in pharmaceutical industries. Protein solubility and stability are the limiting factors for developing such protein drugs. Naturally occurring cyclic peptides and proteins confer superior stability to the linear forms. Backbone cyclization offers a much simple way to improve protein stability compared with other rational or evolutional approaches such as disulfide-bonds engineering or directed evolution. We are using novel intein-based backbone cyclization methods to improve protein stability.

Novel NMR Approaches in Structural Biology.

 Our group is interested in developing new approaches for structural characterization of biomolecules using NMR spectroscopy in order to study important biological phenomena and protein-ligand interactions.

- Segmental Isotope Labeling

We have developed an in vivo segmental isotopic labelling scheme using inteins. Currently, we are expanding the approach to study larger proteins (>25kDa) rapidly, even in vivo.

- Rapid and reliable backbone resonance assignments using metabolic informations.

Protein Structures

 We use NMR spectroscopy ( or crystallography) to determine three-dimensional structures of proteins, which will provide a structural basis to understand structure-function relationships.