The ligand-binding face of the semaphorins revealed by the high-resolution crystal structure of SEMA4D.
Semaphorins, proteins characterized by an extracellular sema domain, regulate axon guidance, immune function and angiogenesis. The crystal structure of SEMA4D (residues 1-657) shows the sema topology to be a seven-bladed beta-propeller, revealing an unexpected homology with integrins. The sema beta-propeller contains a distinctive 77-residue insertion between beta-strands C and D of blade 5. Blade 7 is followed by a domain common to plexins, semaphorins and integrins (PSI domain), which forms a compact cysteine knot abutting the side of the propeller, and an Ig-like domain. The top face of the beta-propeller presents prominent loops characteristic of semaphorins. In addition to limited contact between the Ig-like domains, the homodimer is stabilized through extensive interactions between the top faces in a sector of the beta-propeller used for heterodimerization in integrins. This face of the propeller also mediates ligand binding in integrins, and functional data for semaphorin-receptor interactions map to the equivalent surface.
Love
Christopher A
CA
Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
Harlos
Karl
K
Mavaddat
Nasim
N
Davis
Simon J
SJ
Stuart
David I
DI
Jones
E Yvonne
EY
Esnouf
Robert M
RM
D000595:Amino Acid Sequence; D015703:Antigens, CD; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D039961:Semaphorins
D015703:Antigens, CD; C093224:CD100 antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D039961:Semaphorins