Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self.
Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self.
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DOI：
10.1038/ni.1660
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发表时间：
2008-11
影响因子：
30.5
通讯作者：
Willcox, Benjamin E.
中科院分区：
文献类型：
--
作者：
Mohammed, Fiyaz;Cobbold, Mark;Zarling, Angela L.;Salim, Mahboob;Barrett-Wilt, Gregory A.;Shabanowitz, Jeffrey;Hunt, Donald F.;Engelhard, Victor H.;Willcox, Benjamin E.
蛋白质磷酸化产生一种由主要组织相容性复合体(MHC)I类分子呈递并被T细胞识别的磷酸肽。由于去调节的磷酸化是恶性转化的标志，肿瘤细胞上磷酸化多肽的差异显示提供了一种免疫学上的“转化自我”的标志。在这里，我们证明了磷酸化可以从根本上增加多肽与人类白细胞抗原A2的结合亲和力。为了理解这一点，我们解决了四个磷肽-人类白细胞抗原-A2络合物的晶体结构。这些揭示了一个新的以溶剂暴露的磷酸锚定为中心的多肽结合基序。我们的发现表明，去调控的磷酸化可以通过促进MHC结合或通过影响所呈现表位的抗原同一性来产生新的抗原。这些结果突出了磷酸肽作为癌症免疫治疗新靶点的潜力。
Protein phosphorylation generates a source of phosphopeptides that are presented by major histocompatibility complex (MHC) class I molecules and recognized by T cells. As deregulated phosphorylation is a hallmark of malignant transformation, the differential display of phosphorylated peptides on cancer cells provides an immunological signature of “transformed self”. Here, we demonstrate that phosphorylation can radically increase peptide binding affinity for HLA-A2. To understand this, we solved crystal structures of four phosphopeptide–HLA-A2 complexes. These revealed a novel peptide binding motif centered on a solvent-exposed phosphate anchor. Our findings indicate that deregulated phosphorylation can create neoantigens by promoting MHC binding, or by affecting the antigenic identity of presented epitopes. These results highlight the potential of phosphopeptides as novel targets for cancer immunotherapy.
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影响因子：
19
作者：
Harper, JW
通讯作者：
Harper, JW
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.6
作者：
Gulukota, K;Sidney, J;DeLisi, C
通讯作者：
DeLisi, C
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
人类癌基因组中体细胞突变的模式。
影响因子：
64.8
作者：
Greenman, Christopher;Stephens, Philip;Smith, Raffaella;Dalgliesh, Gillian L.;Hunter, Christopher;Bignell, Graham;Davies, Helen;Teague, Jon;Butler, Adam;Edkins, Sarah;O'Meara, Sarah;Vastrik, Imre;Schmidt, Esther E.;Avis, Tim;Barthorpe, Syd;Bhamra, Gurpreet;Buck, Gemma;Choudhury, Bhudipa;Clements, Jody;Cole, Jennifer;Dicks, Ed;Forbes, Simon;Gray, Kris;Halliday, Kelly;Harrison, Rachel;Hills, Katy;Hinton, Jon;Jenkinson, Andy;Jones, David;Menzies, Andy;Mironenko, Tatiana;Perry, Janet;Raine, Keiran;Richardson, Dave;Shepherd, Rebecca;Small, Alexandra;Tofts, Calli;Varian, Jennifer;Webb, Tony;West, Sofie;Widaa, Sara;Yates, Andy;Cahill, Daniel P.;Louis, David N.;Goldstraw, Peter;Nicholson, Andrew G.;Brasseur, Francis;Looijenga, Leendert;Weber, Barbara L.;Chiew, Yoke-Eng;deFazio, Anna;Greaves, Mel F.;Green, Anthony R.;Campbell, Peter;Birney, Ewan;Easton, Douglas F.;Chenevix-Trench, Georgia;Tan, Min-Han;Khoo, Sok Kean;Teh, Bin Tean;Yuen, Siu Tsan;Leung, Suet Yi;Wooster, Richard;Futreal, P. Andrew;Stratton, Michael R.
通讯作者：
Stratton, Michael R.