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Structural implications of Siglec-5-mediated sialoglycan recognition
Marina A Zhuravleva1, Kathryn Trandem, Peter D Sun
1Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, MD 20852, USA.
Journal of Molecular Biology
|November 21, 2007
Summary
Structural studies of Siglec-5 reveal its mechanism for recognizing sialic acid (Sia) on carbohydrates. This finding suggests Siglec-5 and related receptors exhibit broader sialoglycan recognition than previously known.
Area of Science:
- Immunology
- Structural Biology
- Glycobiology
Background:
- Sialic acid (Sia) Ig-like binding lectins, known as Siglecs, are crucial for myeloid cell recognition and signaling.
- Understanding the molecular mechanisms of Siglec function is essential for deciphering immune responses.
Purpose of the Study:
- To elucidate the molecular mechanism of Siglec-5 (CD170) function by determining its crystal structure.
- To investigate Siglec-5's interaction with sialylated carbohydrates at an atomic level.
Main Methods:
- X-ray crystallography was used to determine the structure of Siglec-5's N-terminal domains.
- Complex structures with alpha(2,3)- and alpha(2,6)-sialyllactose were obtained.
- Surface plasmon resonance (SPR) binding assays were performed.
Main Results:
- The native Siglec-5 structure displayed an unusual CC' loop conformation and a unique interdomain disulfide bond.
- Complexed structures revealed a conserved Sia recognition motif involving Arg124 and the G-strand.
- Limited protein contacts with subterminal sugars were observed, mediated by the GG' linker and CC' loop.
Conclusions:
- Structural and binding data provide mechanistic insights into Siglec-5's linkage-dependent carbohydrate recognition.
- Siglec-5 and related CD33-Siglecs demonstrate broader promiscuity in sialoglycan recognition than previously assumed.
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