6CEZ
Crystal Structure of Rabbit Anti-HIV-1 gp120 V2 Fab 16C2 in complex with V2 peptide ConB
Summary for 6CEZ
| Entry DOI | 10.2210/pdb6cez/pdb |
| Descriptor | Light chain of Fab fragment of rabbit anti-HIV1 gp120 V2 mAb 16C2, Heavy chain of Fab fragment of rabbit anti-HIV1 gp120 V2 mAb 16C2, HIV-1 gp120 V2 Peptide Con B, ... (4 entities in total) |
| Functional Keywords | hiv, gp120, v2, antibody, immune system |
| Biological source | Oryctolagus cuniculus More |
| Total number of polymer chains | 3 |
| Total formula weight | 47607.77 |
| Authors | |
| Primary citation | Lertjuthaporn, S.,Cicala, C.,Van Ryk, D.,Liu, M.,Yolitz, J.,Wei, D.,Nawaz, F.,Doyle, A.,Horowitch, B.,Park, C.,Lu, S.,Lou, Y.,Wang, S.,Pan, R.,Jiang, X.,Villinger, F.,Byrareddy, S.N.,Santangelo, P.J.,Morris, L.,Wibmer, C.K.,Biris, K.,Mason, R.D.,Gorman, J.,Hiatt, J.,Martinelli, E.,Roederer, M.,Fujikawa, D.,Gorini, G.,Franchini, G.,Arakelyan, A.,Ansari, A.A.,Pattanapanyasat, K.,Kong, X.P.,Fauci, A.S.,Arthos, J. Select gp120 V2 domain specific antibodies derived from HIV and SIV infection and vaccination inhibit gp120 binding to alpha 4 beta 7. PLoS Pathog., 14:e1007278-e1007278, 2018 Cited by PubMed Abstract: The GI tract is preferentially targeted during acute/early HIV-1 infection. Consequent damage to the gut plays a central role in HIV pathogenesis. The basis for preferential targeting of gut tissues is not well defined. Recombinant proteins and synthetic peptides derived from HIV and SIV gp120 bind directly to integrin α4β7, a gut-homing receptor. Using both cell-surface expressed α4β7 and a soluble α4β7 heterodimer we demonstrate that its specific affinity for gp120 is similar to its affinity for MAdCAM (its natural ligand). The gp120 V2 domain preferentially engages extended forms of α4β7 in a cation -sensitive manner and is inhibited by soluble MAdCAM. Thus, V2 mimics MAdCAM in the way that it binds to α4β7, providing HIV a potential mechanism to discriminate between functionally distinct subsets of lymphocytes, including those with gut-homing potential. Furthermore, α4β7 antagonists developed for the treatment of inflammatory bowel diseases, block V2 binding to α4β7. A 15-amino acid V2 -derived peptide is sufficient to mediate binding to α4β7. It includes the canonical LDV/I α4β7 binding site, a cryptic epitope that lies 7-9 amino acids amino terminal to the LDV/I, and residues K169 and I181. These two residues were identified in a sieve analysis of the RV144 vaccine trial as sites of vaccine -mediated immune pressure. HIV and SIV V2 mAbs elicited by both vaccination and infection that recognize this peptide block V2-α4β7 interactions. These mAbs recognize conformations absent from the β- barrel presented in a stabilized HIV SOSIP gp120/41 trimer. The mimicry of MAdCAM-α4β7 interactions by V2 may influence early events in HIV infection, particularly the rapid seeding of gut tissues, and supports the view that HIV replication in gut tissue is a central feature of HIV pathogenesis. PubMed: 30153309DOI: 10.1371/journal.ppat.1007278 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.399 Å) |
Structure validation
Download full validation report
