Cryptic association of B7-2 molecules and its implication for clustering

Lankipalli, S and Mahadeva Swamy, HS and Selvam, D and Samanta, D and Nair, D and Ramagopal, UA (2021) Cryptic association of B7-2 molecules and its implication for clustering. In: Protein Science .

	PDF pro_sci_30-09_1958-1973_2021.pdf - Published Version Restricted to Registered users only Download (3MB) | Request a copy
	PDF pro4151-sup-0001-supinfo.docx - Published Supplemental Material Restricted to Registered users only Download (7MB) | Request a copy

Abstract

T-cell co-stimulation through CD28/CTLA4:B7-1/B7-2 axis is one of the extensively studied pathways that resulted in the discovery of several FDA-approved drugs for autoimmunity and cancer. However, many aspects of the signaling mechanism remain elusive, including oligomeric association and clustering of B7-2 on the cell surface. Here, we describe the structure of the IgV domain of B7-2 and its cryptic association into 1D arrays that appear to represent the pre-signaling state of B7-2 on the cell membrane. Super-resolution microscopy experiments on heterologous cells expressing B7-2 and B7-1 suggest, B7-2 form relatively elongated and larger clusters compared to B7-1. The sequence and structural comparison of other B7 family members, B7-1:CTLA4 and B7-2:CTLA-4 complex structures, support our view that the observed B7-2 1D zipper array is physiologically important. This observed 1D zipper-like array also provides an explanation for its clustering, and upright orientation on the cell surface, and avoidance of spurious signaling. © 2021 The Protein Society.

Item Type:	Journal Article
Publication:	Protein Science
Publisher:	Blackwell Publishing Ltd
Additional Information:	The copyright for this article belongs to John Wiley and Sons Inc
Department/Centre:	Division of Biological Sciences > Centre for Neuroscience
Date Deposited:	18 Oct 2021 09:59
Last Modified:	18 Oct 2021 09:59
URI:	http://eprints.iisc.ac.in/id/eprint/69702

Actions (login required)

View Item