4o2c | pdb_00004o2c

An Nt-acetylated peptide complexed with HLA-B*3901

spinqualitylabelsall models 4o2c, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4o2c is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: ACE Related: 4o2e, 4o2f Gene: HLA-B, HLAB (HUMAN), B2M, CDABP0092, HDCMA22P (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation. Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis. Function [1B39_HUMAN] Involved in the presentation of foreign antigens to the immune system. [DDX3X_HUMAN] Multifunctional ATP-dependent RNA helicase. The ATPase activity can be stimulated by various ribo- and deoxynucleic acids indicative for a relaxed substrate specificity. In vitro can unwind partially double stranded DNA with a preference for 5'-single stranded DNA overhangs. Is involved in several steps of gene expression, such as transcription, mRNA maturation, mRNA export and translation. However, the exact mechanisms are not known and some functions may be specific for a subset of mRNAs. Involved in transcriptional regulation. Can enhance transcription from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found associated with the E-cadherin promoter and can down-regulate transcription from the promoter. Involved in regulation of translation initiation. Proposed to be involved in positive regulation of translation such as of cyclin E1/CCNE1 mRNA and specifically of mRNAs containing complex secondary structures in their 5'UTRs; these functions seem to require RNA helicase activity. Specifically promotes translation of a subset of viral and cellular mRNAs carrying a 5'proximal stem-loop structure in their 5'UTRs and cooperates with the eIF4F complex. Proposed to act prior to 43S ribosomal scanning and to locally destabilize these RNA structures to allow recognition of the mRNA cap or loading onto the 40S subunit. After association with 40S ribosomal subunits seems to be involved in the functional assembly of 80S ribosomes; the function seems to cover translation of mRNAs with structured and non-structured 5'UTRs and is independent of RNA helicase activity. Also proposed to inhibit cap-dependent translation by competetive interaction with EIF4E which can block the EIF4E:EIF4G complex formation. Proposed to be involved in stress response and stress granule assembly; the function is independent of RNA helicase activity and seems to involve association with EIF4E. May be involved in nuclear export of specific mRNAs but not in bulk mRNA export via interactions with XPO1 and NXF1. Also associates with polyadenylated mRNAs independently of NXF1. Associates with spliced mRNAs in an exon junction complex (EJC)-dependent manner and seems not to be directly involved in splicing. May be involved in nuclear mRNA export by association with DDX5 and regulating its nuclear location. Involved in innate immune signaling promoting the production of type I interferon (IFN-alpha and IFN-beta); proposed to act as viral RNA sensor, signaling intermediate and transcriptional coactivator. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFN-beta induction. Also found associated with IFN-beta promoters; the function is independent of IRF3. Can bind to viral RNAs and via association with MAVS/IPS1 and DDX58/RIG-I is thought to induce signaling in early stages of infection. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Acts as an antiapoptotic protein through association with GSK3A/B and BIRC2 in an apoptosis antagonizing signaling complex; activation of death receptors promotes caspase-dependent cleavage of BIRC2 and DDX3X and relieves the inhibition. May be involved in mitotic chromosome segregation. Appears to be a prime target for viral manipulations. Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFN-beta induction probably by dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C virus (HCV) replication; the function may involve the association with HCV core protein. HCV core protein inhibits the IPS1-dependent function in viral RNA sensing and may switch the function from a INF-beta inducing to a HCV replication mode. Involved in HIV-1 replication. Acts as a cofactor for XPO1-mediated nuclear export of incompletely spliced HIV-1 Rev RNAs. [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMed As one of the most common posttranslational modifications (PTMs) of eukaryotic proteins, N(alpha)-terminal acetylation (Nt-acetylation) generates a class of N(alpha)-acetylpeptides that are known to be presented by MHC class I at the cell surface. Although such PTM plays a pivotal role in adjusting proteolysis, the molecular basis for the presentation and T cell recognition of N(alpha)-acetylpeptides remains largely unknown. In this study, we determined a high-resolution crystallographic structure of HLA (HLA)-B*3901 complexed with an N(alpha)-acetylpeptide derived from natural cellular processing, also in comparison with the unmodified-peptide complex. Unlike the alpha-amino-free P1 residues of unmodified peptide, of which the alpha-amino group inserts into pocket A of the Ag-binding groove, the N(alpha)-linked acetyl of the acetylated P1-Ser protrudes out of the groove for T cell recognition. Moreover, the Nt-acetylation not only alters the conformation of the peptide but also switches the residues in the alpha1-helix of HLA-B*3901, which may impact the T cell engagement. The thermostability measurements of complexes between N(alpha)-acetylpeptides and a series of MHC class I molecules derived from different species reveal reduced stability. Our findings provide the insight into the mode of N(alpha)-acetylpeptide-specific presentation by classical MHC class I molecules and shed light on the potential of acetylepitope-based immune intervene and vaccine development. Nalpha-terminal acetylation for T cell recognition: molecular basis of MHC class I-restricted nalpha-acetylpeptide presentation.,Sun M, Liu J, Qi J, Tefsen B, Shi Y, Yan J, Gao GF J Immunol. 2014 Jun 15;192(12):5509-19. doi: 10.4049/jimmunol.1400199. Epub 2014 , May 14. PMID:24829406 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-2 microglobulin 3D structures

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