title: Crystal Structure of the Neuropilin-1 MAM Domain: Completing the Neuropilin-1 Ectodomain Picture.
abstract: Neuropilins (NRPs) are single-pass transmembrane receptors involved in several signaling pathways that regulate key physiological processes such as vascular morphogenesis and axon guidance. The MAM domain of NRP, which has previously been implicated in receptor multimerization, was the only portion of the ectopic domain of the NRPs for which the structure, until now, has been elusive. Using site-directed mutagenesis in the linker region preceding the MAM domain we generated a protein construct amenable to crystallization. Here we present the crystal structure of the MAM domain of human NRP1 at 2.24 Å resolution. The protein exhibits a jellyroll topology, with Ca2+ions bound at the inter-strand space enhancing the thermostability of the domain. We show that the MAM domain of NRP1 is monomeric in solution and insufficient to drive receptor dimerization, which leads us to propose a different role for this domain in the context of NRP membrane assembly and signaling.
authors.affiliation: The Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Tamas
authors.initials: T
authors.lastname: Yelland
authors.affiliation: The Institute of Structural and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: s.djordjevic@ucl.ac.uk.
authors.forename: Snezana
authors.initials: S
authors.lastname: Djordjevic
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed / Q000379:methods*; D039942:Neuropilin-1 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C430872:MAML1 protein, human; D014157:Transcription Factors; D039942:Neuropilin-1; D002118:Calcium
keywords: MAM domain; X-ray crystallography; calcium binding; neuropilin; signaling