Structure of metabolic syndrome biomarkers The three-dimensional structure of proteins is vital for understanding their function in health and disease. In this context, European researchers worked to characterise a biomarker of metabolic syndrome. Health © Thinkstock Afamin is a glycoprotein responsible for transporting vitamin E. In patients with metabolic syndrome, afamin levels are elevated, leading to disease parameters such as high blood glucose, hyperlipaemia, obesity and high blood pressure. Despite its high clinical relevance as a disease biomarker, very little is known regarding the structure to function relationship of afamin. The scope of the EU-funded SAXCESS (Structure-function analysis of the human plasma glycoprotein afamin, a potential drug target in the treatment of metabolic syndrome.) project was to determine and analyse the detailed molecular structure of afamin. SAXCESS was technically challenging, and required a multidisciplinary collaboration of experts in areas such as cell biology, medicinal biochemistry, structural biology and structural bioinformatics. Researchers generated multiple variants of the protein with different degrees of glycosylation. They discovered that afamin has the capability of transporting many different low molecular weight molecules in the bloodstream and could thus affect the clearance of therapeutic drugs. As a result, when afamin levels are high, clinicians need to reconsider the levels of drugs that need to be administered. To obtain the three-dimensional structure of afamin, the consortium used antibodies against afamin as scaffolding agents during crystallisation, and developed a lipid cubic phase crystallisation procedure. They have also submitted a follow-up study to the Austrian Science Foundation to elucidate the relation between the structure of afamin and its lipophilic drug transport properties. Furthermore, SAXCESS outcomes led to peer-reviewed publications, invited lectures and conference presentations. In celebration of the International Year of Crystallography 2014, additional public outreach material has been prepared and is available here. Overall, determination of the afamin structure will help understand its functional diversity and allow critical evaluation of its potential as a therapeutic target. Keywords Metabolic syndrome, biomarker, protein, afamin, vitamin E
