Thiru Abarna, Nietlispach Daniel, Mott Helen R, Okuwaki Mitsuru, Lyon Debbie, Nielsen Peter R, Hirshberg Miriam, Verreault Alain, Murzina Natalia V, Laue Ernest D
Department of Biochemistry, Cambridge Centre for Molecular Recognition, University of Cambridge, UK.
EMBO J. 2004 Feb 11;23(3):489-99. doi: 10.1038/sj.emboj.7600088. Epub 2004 Feb 5.
HP1 family proteins are adaptor molecules, containing two related chromo domains that are required for chromatin packaging and gene silencing. Here we present the structure of the chromo shadow domain from mouse HP1beta bound to a peptide containing a consensus PXVXL motif found in many HP1 binding partners. The shadow domain exhibits a novel mode of peptide recognition, where the peptide binds across the dimer interface, sandwiched in a beta-sheet between strands from each monomer. The structure allows us to predict which other shadow domains bind similar PXVXL motif-containing peptides and provides a framework for predicting the sequence specificity of the others. We show that targeting of HP1beta to heterochromatin requires shadow domain interactions with PXVXL-containing proteins in addition to chromo domain recognition of Lys-9-methylated histone H3. Interestingly, it also appears to require the simultaneous recognition of two Lys-9-methylated histone H3 molecules. This finding implies a further complexity to the histone code for regulation of chromatin structure and suggests how binding of HP1 family proteins may lead to its condensation.
HP1家族蛋白是衔接分子，包含两个相关的染色质结构域，这两个结构域是染色质包装和基因沉默所必需的。在此，我们展示了来自小鼠HP1β的染色质影子结构域与一个包含在许多HP1结合伴侣中发现的共有PXVXL基序的肽段结合的结构。影子结构域展现出一种新的肽段识别模式，其中肽段跨二聚体界面结合，夹在来自每个单体的β链之间的β折叠中。该结构使我们能够预测哪些其他影子结构域结合类似的含PXVXL基序的肽段，并为预测其他结构域的序列特异性提供了一个框架。我们表明，除了染色质结构域对赖氨酸-9甲基化组蛋白H3的识别外，将HP1β靶向异染色质还需要影子结构域与含PXVXL的蛋白质相互作用。有趣的是，这似乎还需要同时识别两个赖氨酸-9甲基化组蛋白H3分子。这一发现意味着染色质结构调控的组蛋白密码更加复杂，并提示了HP1家族蛋白的结合可能如何导致其凝聚。
