1KWT

Rat mannose binding protein A (native, MPD)

Summary for 1KWT

• Entry DOI: 10.2210/pdb1kwt/pdb
• Related: 1KWU 1KWV 1KWW 1KWX 1KWY 1KWZ 1KX0 1KX1
• Descriptor: MANNOSE-BINDING PROTEIN A, CALCIUM ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: lectin, c-type lectin, calcium-binding protein, immune system, sugar binding protein
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Secreted: P19999
• Total number of polymer chains: 3
• Total formula weight: 49943.16

Authors

Ng, K.K.S.,Kolatkar, A.R.,Park-Snyder, S.,Feinberg, H.,Clark, D.A.,Drickamer, K.,Weis, W.I. (deposition date: 2002-01-30, release date: 2002-07-05, Last modification date: 2024-11-06)

Primary citation

Ng, K.K.,Kolatkar, A.R.,Park-Snyder, S.,Feinberg, H.,Clark, D.A.,Drickamer, K.,Weis, W.I.
Orientation of bound ligands in mannose-binding proteins. Implications for multivalent ligand recognition.
J.Biol.Chem., 277:16088-16095, 2002

PubMed Abstract: Mannose-binding proteins (MBPs) are C-type animal lectins that recognize high mannose oligosaccharides on pathogenic cell surfaces. MBPs bind to their carbohydrate ligands by forming a series of Ca(2+) coordination and hydrogen bonds with two hydroxyl groups equivalent to the 3- and 4-OH of mannose. In this work, the determinants of the orientation of sugars bound to rat serum and liver MBPs (MBP-A and MBP-C) have been systematically investigated. The crystal structures of MBP-A soaked with monosaccharides and disaccharides and also the structure of the MBP-A trimer cross-linked by a high mannose asparaginyl oligosaccharide reveal that monosaccharides or alpha1-6-linked mannose bind to MBP-A in one orientation, whereas alpha1-2- or alpha1-3-linked mannose binds in an orientation rotated 180 degrees around a local symmetry axis relating the 3- and 4-OH groups. In contrast, a similar set of ligands all bind to MBP-C in a single orientation. The mutation of MBP-A His(189) to its MBP-C equivalent, valine, causes Man alpha 1-3Man to bind in a mixture of orientations. These data combined with modeling indicate that the residue at this position influences the orientation of bound ligands in MBP. We propose that the control of binding orientation can influence the recognition of multivalent ligands. A lateral association of trimers in the cross-linked crystals may reflect interactions within higher oligomers of MBP-A that are stabilized by multivalent ligands.

PubMed: 11850428
DOI: 10.1074/jbc.M200493200

Experimental method

X-RAY DIFFRACTION (1.95 Å)