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Title: The X-ray Crystallographic Structure of Human EAT2 (SH2D1B)

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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Protein and Peptide Letters; Journal Volume: 23; Journal Issue: 10
Country of Publication:
United States

Citation Formats

Taha, Mohammed, Nezerwa, Eric, and Nam, Hyun-Joo. The X-ray Crystallographic Structure of Human EAT2 (SH2D1B). United States: N. p., 2016. Web. doi:10.2174/0929866523666160831162239.
Taha, Mohammed, Nezerwa, Eric, & Nam, Hyun-Joo. The X-ray Crystallographic Structure of Human EAT2 (SH2D1B). United States. doi:10.2174/0929866523666160831162239.
Taha, Mohammed, Nezerwa, Eric, and Nam, Hyun-Joo. 2016. "The X-ray Crystallographic Structure of Human EAT2 (SH2D1B)". United States. doi:10.2174/0929866523666160831162239.
title = {The X-ray Crystallographic Structure of Human EAT2 (SH2D1B)},
author = {Taha, Mohammed and Nezerwa, Eric and Nam, Hyun-Joo},
abstractNote = {},
doi = {10.2174/0929866523666160831162239},
journal = {Protein and Peptide Letters},
number = 10,
volume = 23,
place = {United States},
year = 2016,
month = 9
  • We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobicmore » pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.« less
  • The structure of a crystal complex of the chemically synthesized protease of human immunodeficiency virus 1 with a heptapeptide-derived inhibitor bound in the active site has been determined. The sequence of the inhibitor JG-365 is Ac-Ser-Leu-Asn-Phe-{psi} (CH(OH)CH{sub 2}N)-Pro-Ile-Val-OMe; the K{sub i} is 0.24 nM. The hydroxyethylamine moiety, in place of the normal scissile bond of the substrate, is believed to mimic a tetrahedral reaction intermediate. The structure of the complex has been refined to an R factor of 0.146 at 2.4-{angstrom} resolution by using restrained least squares with rms deviations in bond lengths of 0.02 {angstrom} and bond angles ofmore » 4{degree}. The bound inhibitor diastereomer has the S configuration at the hydroxyethylamine chiral carbon, and the hydroxyl group is positioned between the active site aspartate carboxyl groups within hydrogen bonding distance. Comparison of this structure with a reduced peptide bond inhibitor-protease complex indicates that these contacts confer the exceptional binding strength of JG-365.« less
  • No abstract prepared.
  • No abstract prepared.