1osz

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1osz, resolution 2.1Å

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MHC CLASS I H-2KB HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND AN (L4V) MUTANT OF THE VESICULAR STOMATITIS VIRUS NUCLEOPROTEIN

Overview

The T lineage repertoire is shaped by T cell receptor (TCR)-dependent, positive and negative thymic selection processes. Using TCR-transgenic, (N15tg) beta2-microglobulin-deficient (beta2m-/-) RAG-2(-/-) H-2(b) mice, specific for the VSV8 (RGYVYQGL) octapeptide bound to Kb, we identified a, single weak agonist peptide variant V4L (L4) inducing phenotypic and, functional T cell maturation. The cognate VSV8 peptide, in contrast, triggers negative selection. The crystal structure of L4/Kb was determined, and refined to 2.1 A for comparison with the VSV8/Kb structure at similar, resolution. Aside from changes on the p4 side chain of L4 and the, resulting alteration of the exposed Kb Lys-66 side chain, these two, structures are essentially identical. Hence, a given TCR recognizes subtle, distinctions between highly related ligands, resulting in dramatically, different selection outcomes. Based on these finding and the recent, structural elucidation of the N15-VSV8/Kb complex, moreover, it appears, that the germ-line Valpha repertoire contributes in a significant way to, positive selection.

About this Structure

1OSZ is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

Reference

Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands., Ghendler Y, Teng MK, Liu JH, Witte T, Liu J, Kim KS, Kern P, Chang HC, Wang JH, Reinherz EL, Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10061-6. PMID:9707600

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