The crystal structure of the plexin-semaphorin-integrin domain/hybrid domain/I-EGF1 segment from the human integrin beta2 subunit at 1.8-A resolution.
Integrins are modular (alphabeta) heterodimeric proteins that mediate cell adhesion and convey signals across the plasma membrane. Interdomain motions play a key role in signal transduction by propagating structural changes through the molecule, thus controlling the activation state and adhesive properties of the integrin. We expressed a soluble fragment of the human integrin beta2 subunit comprising the plexin-semaphorin-integrin domain (PSI)/hybrid domain/I-EGF1 fragment and present its crystal structure at 1.8-A resolution. The structure reveals an elongated molecule with a rigid architecture stabilized by nine disulfide bridges. The PSI domain is located centrally and participates in the formation of extended interfaces with the hybrid domain and I-EGF1 domains, respectively. The hybrid domain/PSI interface involves the burial of an Arg residue, and contacts between PSI and I-EGF1 are mainly mediated by well conserved Arg and Trp residues. Conservation of key interacting residues across the various integrin beta subunits sequences suggests that our structure represents a good model for the entire integrin family. Superposition with the integrin beta3 receptor in its bent conformation suggests that an articulation point is present at the linkage between its I-EGF1 and I-EGF2 modules and underlines the importance of this region for the control of integrin-mediated cell adhesion.
Shi
MinLong
M
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Sundramurthy
Kumar
K
Liu
Bin
B
Tan
Suet-Mien
SM
Law
S K Alex
SK
Lescar
Julien
J
D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D018821:CD18 Antigens / Q000737:chemistry*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000737:chemistry*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D039641:Integrin beta Chains / Q000737:chemistry; D016023:Integrins / Q000737:chemistry; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D039961:Semaphorins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014364:Tryptophan / Q000737:chemistry
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D039302:Integrin alphaVbeta3; D039641:Integrin beta Chains; D016023:Integrins; D009419:Nerve Tissue Proteins; D039961:Semaphorins; C091529:plexin; D004815:Epidermal Growth Factor; D014364:Tryptophan; D001120:Arginine