2jhh

From Proteopedia
Revision as of 12:31, 23 January 2008 by OCA (talk | contribs)
Jump to navigation Jump to search
File:2jhh.jpg


2jhh, resolution 1.70Å

Drag the structure with the mouse to rotate

STRUCTURE OF GLOBULAR HEADS OF M-FICOLIN AT ACIDIC PH

OverviewOverview

Ficolins are soluble oligomeric proteins with lectin-like activity, assembled from collagen fibers prolonged by fibrinogen-like recognition, domains. They act as innate immune sensors by recognizing conserved, molecular markers exposed on microbial surfaces and thereby triggering, effector mechanisms such as enhanced phagocytosis and inflammation. In, humans, L- and H-ficolins have been characterized in plasma, whereas a, third species, M-ficolin, is secreted by monocytes and macrophages. To, decipher the molecular mechanisms underlying their recognition properties, we previously solved the structures of the recognition domains of L- and, H-ficolins, in complex with various model ligands (Garlatti et al. (2007), EMBO J. 24: 623-633). We now report the ligand-bound crystal structures of, the recognition domain of M-ficolin, determined at high resolution, (1.75-1.8 A), which provides the first structural insights into its, binding properties. Interaction with acetylated carbohydrates differs from, the one previously described for L-ficolin. This study also reveals the, structural determinants for binding to sialylated compounds, a property, restricted to human M-ficolin and its mouse counterpart, ficolin B., Finally, comparison between the ligand-bound structures obtained at, neutral pH and non-binding conformations observed at pH 5.6 reveals how, the ligand binding site is dislocated at acidic pH. This means that the, binding function of M-ficolin is subject to a pH-sensitive conformational, switch. Considering that the homologous ficolin B is found in the, lysosomes of activated macrophages (Runza et al. (2006) J Endotoxin Res., 12:120-126), we propose that this switch could play a physiological role, in such acidic compartments.

About this StructureAbout this Structure

2JHH is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Sites: and . Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for innate immune sensing by M-ficolin and its control by a pH-dependent conformational switch., Garlatti V, Martin L, Gout E, Reiser JB, Fujita T, Arlaud GJ, Thielens NM, Gaboriaud C, J Biol Chem. 2007 Sep 26;. PMID:17897951

Page seeded by OCA on Wed Jan 23 11:31:09 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA