4AK8

Structure of F241L mutant of langerin carbohydrate recognition domain.

4AK8 の概要

• エントリーDOI: 10.2210/pdb4ak8/pdb
• 分子名称: C-TYPE LECTIN DOMAIN FAMILY 4 MEMBER K, CALCIUM ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: sugar binding protein, langerhans cells, dc-sign, hiv, birbeck granules
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 71845.23

構造登録者

Chabrol, E.,Thepaut, M.,Dezutter-Dambuyant, C.,Vives, C.,Marcoux, J.,Kahn, R.,Valadeau-Guilemond, J.,Vachette, P.,Durand, D.,Fieschi, F. (登録日: 2012-02-22, 公開日: 2013-04-03, 最終更新日: 2024-10-23)

主引用文献

Chabrol, E.,Thepaut, M.,Dezutter-Dambuyant, C.,Vives, C.,Marcoux, J.,Kahn, R.,Valladeau-Guilemond, J.,Vachette, P.,Durand, D.,Fieschi, F.
Alteration of the Langerin Oligomerization State Affects Birbeck Granule Formation.
Biophys.J., 108:666-, 2015

PubMed Abstract: Langerin, a trimeric C-type lectin specifically expressed in Langerhans cells, has been reported to be a pathogen receptor through the recognition of glycan motifs by its three carbohydrate recognition domains (CRD). In the context of HIV-1 (human immunodeficiency virus-1) transmission, Langerhans cells of genital mucosa play a protective role by internalizing virions in Birbeck Granules (BG) for elimination. Langerin (Lg) is directly involved in virion binding and BG formation through its CRDs. However, nothing is known regarding the mechanism of langerin assembly underlying BG formation. We investigated at the molecular level the impact of two CRD mutations, W264R and F241L, on langerin structure, function, and BG assembly using a combination of biochemical and biophysical approaches. Although the W264R mutation causes CRD global unfolding, the F241L mutation does not affect the overall structure and gp120 (surface HIV-1 glycoprotein of 120 kDa) binding capacities of isolated Lg-CRD. In contrast, this mutation induces major functional and structural alterations of the whole trimeric langerin extracellular domain (Lg-ECD). As demonstrated by small-angle x-ray scattering comparative analysis of wild-type and mutant forms, the F241L mutation perturbs the oligomerization state and the global architecture of Lg-ECD. Correlatively, despite conserved intrinsic lectin activity of the CRD, avidity property of Lg-ECD is affected as shown by a marked decrease of gp120 binding. Beyond the change of residue itself, the F241L mutation induces relocation of the K200 side chain also located within the interface between protomers of trimeric Lg-ECD, thereby explaining the defective oligomerization of mutant Lg. We conclude that not only functional CRDs but also their correct spatial presentation are critical for BG formation as well as gp120 binding.

PubMed: 25650933
DOI: 10.1016/J.BPJ.2014.10.075

実験手法

X-RAY DIFFRACTION (1.4 Å)