Crystal structure of the human neuropilin-1 b1 domain.
Neuropilin-1 (Npn-1) is a type I cell surface receptor involved in a broad range of developmental processes, including axon guidance, angiogenesis, and heterophilic cell adhesion. We have determined the crystal structure of the human Npn-1 b1 domain to 1.9 A. The overall structure resembles coagulation factor V and VIII (F5/8) C1 and C2 domains, exhibiting a distorted jellyroll fold. Details of the structure provide insight to b1 domain regions responsible for ligand binding and facilitate rationalization of existing biochemical binding data. A polar cleft formed by adjacent loops at one end of the molecule in conjunction with flanking electronegative surfaces may represent the binding site for the positively charged tails of semaphorins and VEGF(165). The nature of the cell adhesion binding site of the b1 domain can be visualized in context of the structure.
Lee
Christian C
CC
The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Kreusch
Andreas
A
McMullan
Daniel
D
Ng
Ken
K
Spraggon
Glen
G
D000595:Amino Acid Sequence; D001665:Binding Sites; D001779:Blood Coagulation Factors / Q000737:chemistry / Q000235:genetics; D002448:Cell Adhesion / Q000502:physiology; D018360:Crystallography, X-Ray; D006801:Humans; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic; D039942:Neuropilin-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013499:Surface Properties
D001779:Blood Coagulation Factors; D039942:Neuropilin-1