8R8C

Structure of the N-terminal domain of CMA from Cucumis melo in complex with N-acetylgalactosamine

Summary for 8R8C

• Entry DOI: 10.2210/pdb8r8c/pdb
• Related: 8r8a
• Descriptor: Nigrin b-like, CADMIUM ION, 2-acetamido-2-deoxy-beta-D-galactopyranose, ... (5 entities in total)
• Functional Keywords: lectin, beta-trefoil, galactose, n-acetyllactosamine, sugar binding protein
• Biological source: Cucumis melo (muskmelon)
• Total number of polymer chains: 1
• Total formula weight: 14713.04

Authors

Varrot, A. (deposition date: 2023-11-28, release date: 2023-12-27, Last modification date: 2024-10-23)

Primary citation

Lundstrom, J.,Gillon, E.,Chazalet, V.,Kerekes, N.,Di Maio, A.,Feizi, T.,Liu, Y.,Varrot, A.,Bojar, D.
Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin.
Beilstein J Org Chem, 20:306-320, 2024

PubMed Abstract: Plant lectins have garnered attention for their roles as laboratory probes and potential therapeutics. Here, we report the discovery and characterization of agglutinin (CMA1), a new R-type lectin from melon. Our findings reveal CMA1's unique glycan-binding profile, mechanistically explained by its 3D structure, augmenting our understanding of R-type lectins. We expressed CMA1 recombinantly and assessed its binding specificity using multiple glycan arrays, covering 1,046 unique sequences. This resulted in a complex binding profile, strongly preferring C2-substituted, beta-linked galactose (both GalNAc and Fuca1-2Gal), which we contrasted with the established R-type lectin agglutinin 1 (RCA1). We also report binding of specific glycosaminoglycan subtypes and a general enhancement of binding by sulfation. Further validation using agglutination, thermal shift assays, and surface plasmon resonance confirmed and quantified this binding specificity in solution. Finally, we solved the high-resolution structure of the CMA1 N-terminal domain using X-ray crystallography, supporting our functional findings at the molecular level. Our study provides a comprehensive understanding of CMA1, laying the groundwork for further exploration of its biological and therapeutic potential.

PubMed: 38410776
DOI: 10.3762/bjoc.20.31

Experimental method

X-RAY DIFFRACTION (1.55 Å)