Kringle Domain Function

Here we reported the determination of the solution structure of human ror1 kng hror1 kng investigation of its dynamic properties and potential binding interface by nmr spectroscopy.

Kringle domain function. Kringle domains are believed to play a role in binding mediators e g membranes other proteins or phospholipids and in the regulation of proteolytic activity. The kringle fold occurs in combination with other folds in multidomain proteins often as a part of tandem domains 1. 1 2 3 kringle domains 4 5 6 are characterised by a triple loop 3 disulfide bridge structure whose conformation is defined by a number of hydrogen bonds and small pieces of anti parallel beta sheet.

These modules appear to function as independent domains. The recombinant kringle 5 rk5 domain promotes migration and induces apoptosis of proliferating human microvascular endothelial cells hmevc stimulated with bfgf afgf vegf pdgf tgf β1 il 8 or hgf in a dose dependent manner davidson et al 2005. Engineering of a human kringle domain into agonistic and antagonistic binding proteins functioning in vitro and in vivo chang han leea kyung jin parka eun sil sunga aeyung kima ji da choib jeong sun kimc soo hyun kimb myung hee kwond and yong sung kima 1 adepartment of molecular science and technology ajou university san 5 woncheon dong yeongtong gu suwon 443 749 korea.

The amino acid residues important in these kringle ligand binding interactions have been proposed by structural determinations and their relative importance quantified by site directed mutagenesis experimentation. It was suggested that monoclonal antibodies mab against the kringle kng domain of ror1 could induce apoptosis of chronic lymphocytic leukemia cells. Studies using the linear prklydy peptide sequence within the k5 lysine binding site identified grp78 as the endothelial cell surface binding.

Kringle domains have been found in plasminogen hepatocyte growth factors prothrombin and apolipoprotein a. In this study we focused on the region the so called kringle like domain kld that is conserved among species and made a deletion mutant gpnmb δkld. Enhanced expression of wt gpnmb induced sphere and tumor formation in breast epithelial cells.

The kringle family has a broad repertoire of domain partners. Kringle domains are triple disulfide linked domains that function as recognition modules for binding other proteins. Kringles are found throughout the blood clotting and fibrinolytic proteins.

Proteins containing kringle domains such as krm1 have various functions and include proteases growth factors and transmembrane receptors nakamura et al 2001. Genic function has yet to be fully elucidated. Kringle domains consist of approximately 80 amino acid residues with three disulfide bonds.