2LWL

Structural Basis for the Interaction of Human β-Defensin 6 and Its Putative Chemokine Receptor CCR2 and Breast Cancer Microvesicles

2LWL の概要

• エントリーDOI: 10.2210/pdb2lwl/pdb
• NMR情報: BMRB: 18634
• 分子名称: Beta-defensin 106 (1 entity in total)
• 機能のキーワード: breast cancer, dynamic, antimicrobial protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: Q8N104
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5444.38

構造登録者

de Paula, V.S.,Gomes, N.S.F.,Lima, L.G.,Miyamoto, C.A.,Monteiro, R.Q.,Almeida, F.C.L.,Valente, A. (登録日: 2012-08-02, 公開日: 2013-08-21, 最終更新日: 2024-10-30)

主引用文献

De Paula, V.S.,Gomes, N.S.,Lima, L.G.,Miyamoto, C.A.,Monteiro, R.Q.,Almeida, F.C.,Valente, A.P.
Structural Basis for the Interaction of Human beta-Defensin 6 and Its Putative Chemokine Receptor CCR2 and Breast Cancer Microvesicles.
J.Mol.Biol., 425:4479-4495, 2013

PubMed Abstract: Human β-defensins (hBDs) are believed to function as alarm molecules that stimulate the adaptive immune system when a threat is present. In addition to its antimicrobial activity, defensins present other activities such as chemoattraction of a range of different cell types to the sites of inflammation. We have solved the structure of the hBD6 by NMR spectroscopy that contains a conserved β-defensin domain followed by an extended C-terminus. We use NMR to monitor the interaction of hBD6 with microvesicles shed by breast cancer cell lines and with peptides derived from the extracellular domain of CC chemokine receptor 2 (Nt-CCR2) possessing or not possessing sulfation on Tyr26 and Tyr28. The NMR-derived model of the hBD6/CCR2 complex reveals a contiguous binding surface on hBD6, which comprises amino acid residues of the α-helix and β2-β3 loop. The microvesicle binding surface partially overlaps with the chemokine receptor interface. NMR spin relaxation suggests that free hBD6 and the hBD6/CCR2 complex exhibit microsecond-to-millisecond conformational dynamics encompassing the CCR2 binding site, which might facilitate selection of the molecular configuration optimal for binding. These data offer new insights into the structure-function relation of the hBD6-CCR2 interaction, which is a promising target for the design of novel anticancer agents.

PubMed: 23938203
DOI: 10.1016/j.jmb.2013.08.001

実験手法

SOLUTION NMR