5U3P

Crystal Structure of DH511.4 Fab

Summary for 5U3P

• Entry DOI: 10.2210/pdb5u3p/pdb
• Related: 5U3J 5U3K 5U3L 5U3M 5U3N 5U3O
• Descriptor: DH511.4 Fab Heavy Chain, DH511.4 Fab Light Chain (3 entities in total)
• Functional Keywords: hiv-1, neutralizing, antibody, gp41, mper, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48400.01

Authors

Nicely, N.I.,Williams, L.D.,Ofek, G.,Haynes, B.F. (deposition date: 2016-12-02, release date: 2017-02-15, Last modification date: 2024-10-23)

Primary citation

Williams, L.D.,Ofek, G.,Schatzle, S.,McDaniel, J.R.,Lu, X.,Nicely, N.I.,Wu, L.,Lougheed, C.S.,Bradley, T.,Louder, M.K.,McKee, K.,Bailer, R.T.,O'Dell, S.,Georgiev, I.S.,Seaman, M.S.,Parks, R.J.,Marshall, D.J.,Anasti, K.,Yang, G.,Nie, X.,Tumba, N.L.,Wiehe, K.,Wagh, K.,Korber, B.,Kepler, T.B.,Munir Alam, S.,Morris, L.,Kamanga, G.,Cohen, M.S.,Bonsignori, M.,Xia, S.M.,Montefiori, D.C.,Kelsoe, G.,Gao, F.,Mascola, J.R.,Moody, M.A.,Saunders, K.O.,Liao, H.X.,Tomaras, G.D.,Georgiou, G.,Haynes, B.F.
Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.
Sci Immunol, 2:-, 2017

PubMed Abstract: Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1-specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1-infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.

PubMed: 28783671
DOI: 10.1126/sciimmunol.aal2200

Experimental method

X-RAY DIFFRACTION (1.5 Å)