Oxford University Department of Biochemistry
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Martin Noble
Structural studies on regulatory proteins

Co-workers: Dr. Maria Hoellerer (JRF, St. Cross College), Dr. John Sinclair, Dr. Max Soegaard, Eugene Valkov, Sonja Lorentz, Helen Fielder, Marc Morgan

Work in this group addresses structure-function relationships of medically important proteins from two areas: adhesive cellular interactions and the eukaryotic cell cycle. We study these proteins by both experimental and computational approaches. Experimentally, proteins are subject to structural, biochemical and biophysical characterisation. Development of computational methods has centred on making tools for drug design and molecular surface analysis. We are also applying protein design to prepare novel biomaterials that are ordered on the nanometre scale. Regulation of both cellular adhesion and the cell cycle depends on protein modifications and reversible protein:protein interactions to mediate an appropriate response within highly interdependent systems (e.g. Figure 1). Our approach is to characterize the structures and interactions of key proteins within such networks. For example, we have studied the structure and interactions of paxillin, a protein responsible for recruiting several proteins into focal adhesion complexes.

Similarly, we have recently described the structure of the complex between hyaluronan (HA) and CD44, its major cell-surface receptor (Figure 2). This complex represents an important example of how a cell recognizes saccharide components of the ECM. The structure has revealed the atomic details of an interaction that is a potential target for drug design, and has suggested a mechanism to explain the regulation of CD44-HA interactions.

To characterize such structures, we have made tools for visualizing and analyzing protein surfaces. These tools allow the flexible mapping of properties onto a protein surface, and have been integrated into the CCP4MG program (Figure 3).

In the area of protein design, we have developed a general approach to the formation of robust protein arrays (e.g. Figure 4). These arrays are made from fusion proteins, chosen so as to exploit the stabilizing forces of symmetrical macromolecular complexes. We are exploring the properties and applications of the resulting materials.


Research Images

Figure 1: Some of the proteins and interactions observed in focal adhesion complexes

Figure 2: Atomic details of the interaction between hyaluronan and CD44

Figure 3: Hydrophobic surface revealing the molecular recognition site of an SH3 domain

Figure 4: Design of a protein-lattice based upon fusion of the proteins PurE and human ferritin

Contact: martin.noble@bioch.ox.ac.uk

Graduate Student and Postdoctoral Positions: Enquiries with CV welcome

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