Crystal Structures of Human C4.4A Reveal the Unique Association of Ly6/uPAR/α-neurotoxin Domain
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Crystal Structures of Human C4.4A Reveal the Unique Association of Ly6/uPAR/α-neurotoxin Domain. / Jiang, Yunbin; Lin, Lin; Chen, Shanli; Jiang, Longguang; Kriegbaum, Mette C; Gårdsvoll, Henrik; Hansen, Line V; Li, Jinyu; Ploug, Michael; Yuan, Cai; Huang, Mingdong.
In: International Journal of Biological Sciences, Vol. 16, No. 6, 2020, p. 981-993.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Crystal Structures of Human C4.4A Reveal the Unique Association of Ly6/uPAR/α-neurotoxin Domain
AU - Jiang, Yunbin
AU - Lin, Lin
AU - Chen, Shanli
AU - Jiang, Longguang
AU - Kriegbaum, Mette C
AU - Gårdsvoll, Henrik
AU - Hansen, Line V
AU - Li, Jinyu
AU - Ploug, Michael
AU - Yuan, Cai
AU - Huang, Mingdong
N1 - © The author(s).
PY - 2020
Y1 - 2020
N2 - Ly6/uPAR/α-neurotoxin domain (LU-domain) is characterized by the presence of 4-5 disulfide bonds and three flexible loops that extend from a core stacked by several conversed disulfide bonds (thus also named three-fingered protein domain). This highly structurally stable protein domain is typically a protein-binder at extracellular space. Most LU proteins contain only single LU-domain as represented by Ly6 proteins in immunology and α-neurotoxins in snake venom. For Ly6 proteins, many are expressed in specific cell lineages and in differentiation stages, and are used as markers. In this study, we report the crystal structures of the two LU-domains of human C4.4A alone and its complex with a Fab fragment of a monoclonal anti-C4.4A antibody. Interestingly, both structures showed that C4.4A forms a very compact globule with two LU-domain packed face to face. This is in contrast to the flexible nature of most LU-domain-containing proteins in mammals. The Fab combining site of C4.4A involves both LU-domains, and appears to be the binding site for AGR2, a reported ligand of C4.4A. This work reports the first structure that contain two LU-domains and provides insights on how LU-domains fold into a compact protein and interacts with ligands.
AB - Ly6/uPAR/α-neurotoxin domain (LU-domain) is characterized by the presence of 4-5 disulfide bonds and three flexible loops that extend from a core stacked by several conversed disulfide bonds (thus also named three-fingered protein domain). This highly structurally stable protein domain is typically a protein-binder at extracellular space. Most LU proteins contain only single LU-domain as represented by Ly6 proteins in immunology and α-neurotoxins in snake venom. For Ly6 proteins, many are expressed in specific cell lineages and in differentiation stages, and are used as markers. In this study, we report the crystal structures of the two LU-domains of human C4.4A alone and its complex with a Fab fragment of a monoclonal anti-C4.4A antibody. Interestingly, both structures showed that C4.4A forms a very compact globule with two LU-domain packed face to face. This is in contrast to the flexible nature of most LU-domain-containing proteins in mammals. The Fab combining site of C4.4A involves both LU-domains, and appears to be the binding site for AGR2, a reported ligand of C4.4A. This work reports the first structure that contain two LU-domains and provides insights on how LU-domains fold into a compact protein and interacts with ligands.
U2 - 10.7150/ijbs.39919
DO - 10.7150/ijbs.39919
M3 - Journal article
C2 - 32140067
VL - 16
SP - 981
EP - 993
JO - International Journal of Biological Sciences
JF - International Journal of Biological Sciences
SN - 1449-2288
IS - 6
ER -
ID: 244688346