4KU1

Role of the hinge and C-gamma-2/C-gamma-3 interface in immunoglobin G1 Fc domain motions: implications for Fc engineering

4KU1 の概要

• エントリーDOI: 10.2210/pdb4ku1/pdb
• 分子名称: Ig gamma-1 chain C region, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[beta-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: human fc fragment, immune response, immune system
• 由来する生物種: HOMO SAPIENS (human)
• 細胞内の位置: Secreted: P01857
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50876.70

構造登録者

Frank, M.,Walker, R.,Lanzilotta, W.N.,Prestegard, J.H.,Barb, A.W. (登録日: 2013-05-21, 公開日: 2014-02-19, 最終更新日: 2024-11-27)

主引用文献

Frank, M.,Walker, R.C.,Lanzilotta, W.N.,Prestegard, J.H.,Barb, A.W.
Immunoglobulin g1 fc domain motions: implications for fc engineering.
J.Mol.Biol., 426:1799-1811, 2014

PubMed Abstract: The fragment crystallizable (Fc) region links the key pathogen identification and destruction properties of immunoglobulin G (IgG). Pathogen opsonization positions Fcs to activate pro-inflammatory Fcγ receptors (FcγRs) on immune cells. The cellular response and committal to a damaging, though protective, immune response are tightly controlled at multiple levels. Control mechanisms are diverse and in many cases unclear, but one frequently suggested contribution originates in FcγR affinity being modulated through shifts in Fc conformational sampling. Here, we report a previously unseen IgG1 Fc conformation. This observation motivated an extensive molecular dynamics investigation of polypeptide and glycan motions that revealed greater amplitude of motion for the N-terminal Cγ2 domains and N-glycan than previously observed. Residues in the Cγ2/Cγ3 interface and disulfide-bonded hinge were identified as influencing the Cγ2 motion. Our results are consistent with a model of Fc that is structurally dynamic. Conformational states that are competent to bind immune-stimulating FcγRs interconverted with Fc conformations distinct from those observed in FcγR complexes, which may represent a transient, nonbinding population.

PubMed: 24522230
DOI: 10.1016/j.jmb.2014.01.011

実験手法

X-RAY DIFFRACTION (1.9 Å)