Solution structure and sugar-binding mechanism of mouse latrophilin-1 RBL: a 7TM receptor-attached lectin-like domain.
Latrophilin-1 (Lat-1), a target receptor for alpha-Latrotoxin, is a putative G protein-coupled receptor implicated in synaptic function. The extracellular portion of Lat-1 contains a rhamnose binding lectin (RBL)-like domain of unknown structure. RBL domains, first isolated from the eggs of marine species, are also found in the ectodomains of other metazoan transmembrane proteins, including a recently discovered coreceptor of the neuronal axon guidance molecule SLT-1/Slit. Here, we describe a structure of this domain from the mouse Lat-1. RBL adopts a unique alpha/beta fold with long structured loops important for monosaccharide recognition, as shown in the structure of a complex with L-rhamnose. Sequence alignments and mutagenesis show that residues important for carbohydrate binding are often absent in other receptor-attached examples of RBL, including the SLT-1/Slit coreceptor. We postulate that this domain class facilitates direct protein-protein interactions in many transmembrane receptors.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, United Kingdom. ioannis.vakonakis@bioch.ox.ac.uk
Ioannis
I
Vakonakis
Tobias
T
Langenhan
Simone
S
Prömel
Andreas
A
Russ
Iain D
ID
Campbell
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D037102:Lectins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000737:chemistry* / Q000235:genetics; D012210:Rhamnose / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012996:Solutions
C530747:Adgrl1 protein, mouse; D002241:Carbohydrates; D037102:Lectins; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012996:Solutions; D012210:Rhamnose