Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains.
The three-dimensional structure of the ligand-binding region of human E-selectin has been determined at 2.0 A resolution. The structure reveals limited contact between the two domains and a coordination of Ca2+ not predicted from other C-type lectins. Structure/function analysis indicates a defined region and specific amino-acid side chains that may be involved in ligand binding. These features of the E-selectin/ligand interaction have important implications for understanding the recruitment of leukocytes to sites of inflammation.
Graves
B J
BJ
Roche Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.
Crowther
R L
RL
Chandran
C
C
Rumberger
J M
JM
Li
S
S
Huang
K S
KS
Presky
D H
DH
Familletti
P C
PC
Wolitzky
B A
BA
Burns
D K
DK
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D006224:Cricetinae; D018360:Crystallography, X-Ray; D019040:E-Selectin; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism; D016256:Lewis X Antigen / Q000737:chemistry; D008024:Ligands; D037241:Mannose-Binding Lectins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D037102:Lectins; D016256:Lewis X Antigen; D008024:Ligands; D037241:Mannose-Binding Lectins; D004815:Epidermal Growth Factor