Structure of a VLR-like protein Bf66946 from Branchiostoma floridae provides insights into the evolution of adaptive immune system in jawless vertebrates

【作者】 曹冬冬； 成望； 江永亮； 汪文捷； 李琼； 周丛照；

【机构】 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China；

【摘要】 With the increase of population with auto-immunity diseases today,more and more researchesare focused on the origination of adaptive immunity in vertebrates.The characterizationof the variable lymphocyte receptors(VLRs)consisting of leucine-rich repeats(LRRs)in agnathans(jawless fish)has brought the origin of adaptive immunity forward to500 Mya ago when the vertebrate starts to appear.Recently,amphioxus at the basal positionof the chordate phylum was reported to hold extraordinary innate complexity and diversity,which was therefore named as"the explosion of immunity".Moreover,some researchershave found some evidence of the existence of adaptive immunity related moleculesin amphioxus.In this study,we screened out nine LRR-only proteins from Branchiostomafloridae on the basis of sequence analysis.Among these proteins,the threedimensionalstructure of Bf66946 was determined at 1.60 ? resolution by X-ray crystallography.Sequence and structural analysis reveals that Bf66946 is a VLR-like protein andshows homologous to VLRC rather than either VLRA or VLRB.Similar to the structure-known VLRs,Bf66946 also forms a horseshoe-shaped right-handed solenoidal structure.Differently,the CP in Bf66946 has an extra of 8 amino-acid residues and folds into aα-helix.The electrostatic potentials analysis displays an electron-negative region within theconcave surface of the LRR solenoid structure which is suggested as the ligand-bindingsite,implying its recognized ligand might be electron-positive.Afterwards,the bacterialbinding assay showed that Bf66946 can attach to the surface of S.aureus and S.pneumonia(Gram-positive bacteria),but not to E.coli(Gram-negative bacteria).This observationsuggests that Bf66946 could recognize the ligands which are characteristically displayedon the surface of Gram-positive bacteria.Altogether,the provided in our study gives insightsinto the existence of adaptive immunity in amphioxus,making a deep understandingto the evolution of adaptive immune system in jawless vertebrates.更多还原

【Abstract】 With the increase of population with auto-immunity diseases today,more and more researchesare focused on the origination of adaptive immunity in vertebrates.The characterizationof the variable lymphocyte receptors(VLRs)consisting of leucine-rich repeats(LRRs)in agnathans(jawless fish)has brought the origin of adaptive immunity forward to500 Mya ago when the vertebrate starts to appear.Recently,amphioxus at the basal positionof the chordate phylum was reported to hold extraordinary innate complexity and diversity,which was therefore named as"the explosion of immunity".Moreover,some researchershave found some evidence of the existence of adaptive immunity related moleculesin amphioxus.In this study,we screened out nine LRR-only proteins from Branchiostomafloridae on the basis of sequence analysis.Among these proteins,the threedimensionalstructure of Bf66946 was determined at 1.60 ? resolution by X-ray crystallography.Sequence and structural analysis reveals that Bf66946 is a VLR-like protein andshows homologous to VLRC rather than either VLRA or VLRB.Similar to the structure-known VLRs,Bf66946 also forms a horseshoe-shaped right-handed solenoidal structure.Differently,the CP in Bf66946 has an extra of 8 amino-acid residues and folds into aα-helix.The electrostatic potentials analysis displays an electron-negative region within theconcave surface of the LRR solenoid structure which is suggested as the ligand-bindingsite,implying its recognized ligand might be electron-positive.Afterwards,the bacterialbinding assay showed that Bf66946 can attach to the surface of S.aureus and S.pneumonia(Gram-positive bacteria),but not to E.coli(Gram-negative bacteria).This observationsuggests that Bf66946 could recognize the ligands which are characteristically displayedon the surface of Gram-positive bacteria.Altogether,the provided in our study gives insightsinto the existence of adaptive immunity in amphioxus,making a deep understandingto the evolution of adaptive immune system in jawless vertebrates.更多还原