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Crystal structure of the human MBL-associated protein 19 (MAp19)
Structural highlights
DiseaseMASP2_HUMAN Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:613791. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.[1] [2] FunctionMASP2_HUMAN Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.[3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMAp19 is an alternative splicing product of the MASP-2 gene comprising the N-terminal CUB1-epidermal growth factor (EGF) segment of MASP-2, plus four additional residues at its C-terminal end. Like full-length MASP-2, it forms Ca(2+)-dependent complexes with mannan-binding lectin (MBL) and L-ficolin. The x-ray structure of human MAp19 was solved to a resolution of 2.5 A. It shows a head to tail homodimer held together by interactions between the CUB1 module of one monomer and the EGF module of its counterpart. A Ca(2+) ion bound to each EGF module stabilizes the dimer interfaces. A second Ca(2+) ion is bound to the distal end of each CUB1 module, through six ligands contributed by Glu(52), Asp(60), Asp(105), Ser(107), Asn(108), and a water molecule. Compared with its counterpart in human C1s, the N-terminal end of the MAp19 CUB1 module contains a 7-residue extension that forms additional inter-monomer contacts. To identify the residues involved in the interaction of MAp19 with MBL and L-ficolin, point mutants were generated and their binding ability was determined using surface plasmon resonance spectroscopy. Six mutations at Tyr(59), Asp(60), Glu(83), Asp(105), Tyr(106), and Glu(109) either strongly decreased or abolished interaction with both MBL and L-ficolin. These mutations map a common binding site for these proteins located at the distal end of each CUB1 module and stabilized by the Ca(2+) ion. The X-ray structure of human mannan-binding lectin-associated protein 19 (MAp19) and its interaction site with mannan-binding lectin and L-ficolin.,Gregory LA, Thielens NM, Matsushita M, Sorensen R, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C J Biol Chem. 2004 Jul 9;279(28):29391-7. Epub 2004 Apr 26. PMID:15117939[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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