This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

Human Fab PG16

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal structure of human Fab PG16, a broadly reactive and potent HIV-1 neutralizing antibody (3mug)

About this Structure

3mug is a 12 chains structure with sequences from Homo sapiens. Full crystallographic information is available from OCA.

HIV-1 vaccination has remained an elusive goal primarily due to the difficulty in finding broadly neutralizing antibodies (bNAb) responses targeting the envelope glycoproteins of HIV-1, gp120 and gp41. PG9 and PG16 are exciting new monoclonal antibodies (mAbs) which have shown approximately an order of magnitude higher potency against HIV-1 viral particles than previously described mAbs.

Upon investigation of the antigen binding fragment (Fab) of PG16, researchers discovered that the monoclinic crystals of PG16 Fab contain six Fab molecules in the asymmetric unit with three chemically distinct environments ^[1]. The unusually long, 28-residue CDR H3 has a canonical, β-bulge torso conformation which forms a unique, hammerhead structure that towers above the antibody surface ^[2]. It is believed that this unique hammerhead structure might play a significant role in HIV-1 trimeric surface envelope glycoprotein (Env) binding and neutralization ^[1]. Another unusual attribute is that CDR H3 protrudes from the antibody and folds as a semi-independent sub-domain. In the few observed structural homologs, the "hammerhead" or "axe" motif is used as a structural building block and is an integral part of other domains ^[3].

It is postulated that the very long CDR H3 loops can form subdomains which impart much of the specificity and affinity of the antibody. After exchange of small residue stretches in loop 1 of H3 between PG9 and PG16 it was observed that the PG16 swap variant mimicked the neutralization profile of PG9. In addition to the unusual CDR H3 subdomain, researchers have found that PG16 and PG9 both demonstrate unusual N-linked glycosylation and extensive affinity maturation ^[3] Structural studies have suggested that it is these two attributes, extensive affinity maturation and the CRD H3 loops, which are the most important elements involved in PG16 and PG9 potency against HIV ^[3].

See Antibody for additional structural information.

References

↑ ^1.0 ^1.1 Robert Pejchal, Laura M. Walker, Robyn L. Stanfield, Sanjay K. Phogat, Wayne C. Koff, Pascal Poignard,Dennis R. Burton, and Ian A. Wilson. Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1. Proc Natl Acad Sci U S A. 2010 June 22; 107(25): 11483–11488. PMCID: PMC2895122.
↑ Al-Lazikani B, Lesk AM, Chothia C. Standard conformations for the canonical structures of immunoglobulins. J Mol Biol. 1997 Nov 7;273(4):927-48. PMID:9367782 doi:10.1006/jmbi.1997.1354
↑ ^3.0 ^3.1 ^3.2 Pancera M, McLellan JS, Wu X, Zhu J, Changela A, Schmidt SD, Yang Y, Zhou T, Phogat S, Mascola JR, Kwong PD. Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1. J Virol. 2010 Aug;84(16):8098-110. Epub 2010 Jun 10. PMID:20538861 doi:10.1128/JVI.00966-10

Created with the participation of Duncan Renfrow-Symon, David Canner.

Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Human_Fab_PG16"

@@ Line 1: / Line 1: @@
+<StructureSection load="3mug" size="400" color="" frame="true"  spin="on" Scene=  side="right" caption= >
 [[Image:3mug.jpg|left|200px]]
-<!--
+===Crystal structure of human Fab PG16, a broadly reactive and potent HIV-1 neutralizing antibody ([[3mug]])===
-The line below this paragraph, containing "STRUCTURE_3mug", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_3mug|  PDB=3mug  |  SCENE=  }}
-===Crystal structure of human Fab PG16, a broadly reactive and potent HIV-1 neutralizing antibody===
 ==About this Structure==
-MUG is a 12 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MUG OCA].
+[[3mug]] is a 12 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MUG OCA].
@@ Line 26: / Line 19: @@
 See [[Antibody]] for additional structural information.
+</StructureSection>
 ==References==
@@ Line 41: / Line 34: @@
 [[Category: Pg16]]
 [[Category: Sulfotyrosine]]
+<br />
+Created with the participation of [[User:Duncan Renfrow-Symon|Duncan Renfrow-Symon]], [[User:David Canner|David Canner]].

Human Fab PG16

From Proteopedia

Current revision

Crystal structure of human Fab PG16, a broadly reactive and potent HIV-1 neutralizing antibody (3mug)

About this Structure

References

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox