In 1961 Jürgen Engel started his research on extracellular matrix and cell adhesion with a project on collagen. He studied its physical properties, composition and folding from the three constituent chains. In 1961 only a single collagen was known but today the collagen family has grown to 27 members. They all consist of three identical or diffent polypeptide chains, which are connected by one or several rod-like triple helical segments. These are flanked or interrupted by in part globular domains with different functions. During his entire career, Jürgen Engel and members of his group explored various collagen related problems, in part in collaborations with the research group of Hans Peter Bächinger, Shriners Hospital Portland Oregon. It was found that the folding oft collagens to their native structures is quite different from that of other proteins. It is governed by the slow cis-trans isomerization of peptide bonds adjacent to proline and hydroxyproline, which occur very frequently in X- and Y-positions of the typical Gly-X-Y sequences in triple helical regions. The proper chain composition of a collagen is achieved by the selective association of C-terminal globular domains, named trimerization domains. A prominent feature of collagen folding is a strong hysteresis, which was systematically explored by model peptides with repeating Gly-X-Y sequences.
Non-collagenous structures, which also lead to multichain assembly attracted the interest of the group. These are the α–helical coiled coil structures. In the cytosol two-stranded coil-coils predominate, whereas in the extacellular space many proteins contain two or three stranded coiled coils. In cartilage oligomeric protein (COMP), a collagen binding protein, even a five-stranded coiled-coil was found. The x-ray structure of this unusual domain was solved. Its coiled-coil structure contains a rather wide hydrophobic channel and it was speculated that the channel may serve as binding site for hydrophobic compounds like vitamin D.
Very fruitful was the investigation of the minicollagens of sweet water hydra, performed in collaboration with Thomas Holstein, Zoological Institute University Heidelberg. The minicollagens are the smalles collagens known. Together with other proteins they form the capsules of a shooting organel called nematocyst. The capsule wall is a very dense structure, which withstands 150 atmospheres of osmotic pressure needed to expel the shooting device at very high speed.
Another family of extracellular matrix proteins, which was studied in detail by the group of Jürgen Engel are the laminins. In collaboration with the group of Rupert Timpl, Munich the cross-shaped structure and domain organization of these proteins was elucidated. Several laminins form protein layers called basement membranes together with collagen IV and proteoglycans. Laminins like the collagens are multifunctional multidomain proteins. An important function of laminins is cell attachment the specificity of which comes from cell receptors of the integrin class. Integrins are transmembrane receptors and it was possible to reconstitute them into lipid vesicles. In comparison to the laminins the shape and dynamics of fibronectin was studied by the group of Engel. In this context also the work on agrin, performed in collaboration with Markus Ruegg, Biozentrum, should be mentioned.
A large amount of work was invested into a molecular understanding of the homo- and heteroassociation of adhesion molecules of the cadherin family. Two different modes of interactions (cis within a lipid membrane and trans between membranes) were defined by x-ray crystallography, nuclear magnetic resonance and electron microscopy. Important for this work were collaboration with the group of Rolf Kemler, Max Planck Institut für Immunologie, Freiburg Breisgau and Stefan Grzesiek, Biozentrum, Basel.
Very recently the interest of Jürgen Engel turned to the question how the extracellular matrix directs mineralization, for example in the formation of dentine and muscle shells. He served as a lecturer at the Göttingen Spirit Summer School in Biological Research in Dentistry and several other places.
This summary of different projects is very short and incomplete. A complete picture oft the research activites of Jürgen Engels group will be obtained from the publicstion list.
