5IMK

Nanobody targeting human Vsig4 in Spacegroup C2

Summary for 5IMK

• Entry DOI: 10.2210/pdb5imk/pdb
• Related: 5IML 5IMM 5IMO
• Descriptor: Nanobody, V-set and immunoglobulin domain-containing protein 4 (3 entities in total)
• Functional Keywords: nanobody, complement receptor, vsig4 crig, immune system
• Biological source: Camelidae; More
• Cellular location: Membrane ; Single-pass type I membrane protein : Q9Y279
• Total number of polymer chains: 2
• Total formula weight: 39205.79

Authors

Wen, Y. (deposition date: 2016-03-06, release date: 2017-01-11, Last modification date: 2024-10-23)

Primary citation

Wen, Y.,Ouyang, Z.,Schoonooghe, S.,Luo, S.,De Baetselier, P.,Lu, W.,Muyldermans, S.,Raes, G.,Zheng, F.
Structural evaluation of a nanobody targeting complement receptor Vsig4 and its cross reactivity
Immunobiology, 222:807-813, 2017

PubMed Abstract: Vsig4 is a recently identified immune regulatory protein related to the B7 family with dual functionality: a negative regulator of T cell activation and a receptor for the complement components C3b and C3c. Here we present a structural evaluation of a nanobody, Nb119, against the extracellular IgV domain protein of both mouse and human recombinant Vsig4, which have a high degree of sequence identity. Although mouse and human Vsig4 bind to Nb119 with a 250 times difference in dissociation constants, the interaction results in a highly identical assembly with a RMSD of 0.4Å. The molecular determinants for Vsig4 recognition and cross reactivity unveiled by the atomic structure of Nb119 in complex with mVsig4 and hVsig4 afford new insights useful for the further optimization of the nanobody for potential use in humans. Additionally, structural analysis of the Vsig4-Nb119 complexes indicates that Nb119 occupies the interface on Vsig4 recognized by the macroglobulin-like domains MG4 and MG5 of C3b. Thus an affinity-improved Nb119 may have the potential to influence the activation of both T cells and complement.

PubMed: 27889311
DOI: 10.1016/j.imbio.2016.11.008

Experimental method

X-RAY DIFFRACTION (1.227 Å)