Angiogenesis and rhodopsin-like receptors: a role for N-terminal acidic residues?
Numerous rhodopsin-like G-protein coupling receptors induce or inhibit angiogenesis. The active human receptors include several chemokine receptors, apelin APJ receptor, neuropeptide Y Y2 receptor, Duffy antigen, and herpes virus-8 receptor. A common and striking feature of these receptors is the large fraction (up to 42%) of residues with anionic sidechains (Asp, Glu, and benzene anions Tyr, Trp, and Phe) in the N-terminal extracellular domain. These residues (which are frequently clustered) can assist the binding of ligand peptides, but should also support interactions that help tubular arraying of cells, e.g., via cationic bridges and/or hydrogen bonding with cell-connecting receptors such as integrins, or with proteins of the extracellular matrix.
Parker
Steven L
SL
Department of Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. slparker@utmem.edu
Parker
Michael S
MS
Sah
Renu
R
Sallee
Floyd
F
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D042501:Angiogenic Proteins / Q000737:chemistry*; D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D012243:Rhodopsin / Q000737:chemistry*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship
D000596:Amino Acids; D042501:Angiogenic Proteins; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin