Low density lipoprotein receptor domains (LDLrs) represent a large cell surface receptor superfamily of consensus length 39 residues. Alignment of 194 sequences indicated highly conserved Cys and Asp/Glu residues, and a consensus secondary structure with three fl-strands was predicted. Sequence threading against known protein folds indicated consistency with small flsheet proteins. Complement factor I contains two LDLrs, and the second of these was successfully expressed using a bacterial pGEX system. FT-IR spectroscopy on this indicated a small amount of fl-sheet together with turns and loops. LDLr is proposed to have a fl-sheet structure in which the five biologically important Asp/Glu residues are located on an exposed loop.Key words: LDLr domain; FT-IR spectroscopy; Secondary structure prediction; Protein fold recognition; fl-Sheet protein basic amino acids in other ligands [2]. LDLr-3 to LDLr-7 in the LDL receptor are essential for apoprotein B binding, and LDLr-5 is essential for apoprotein E binding. In the ~2M receptor, a fragment with eight LDLr domains binds to ~2 M.A powerful strategy to analyse protein structures has been developed, based on the joint use of (a) averaged secondary structure predictions to define structural elements, (b) sequence threading against known protein folds to identify related protein folds, and (c) spectroscopy to identify the secondary structure [6,7]. By this approach, we show that LDLr contains turns and loops with a small amount of fl-strand, and propose that the biologically important Asp/Glu residues are located on a surface loop.