Structural and Functional Analysis of Two Parvalbumins of Extramuscular Origin

小白蛋白最初被鉴定为横纹肌中的钙结合细胞质蛋白，在那里它们被认为是钙缓冲剂。本研究的主题是来自非肌肉组织的小白蛋白家族的两个成员的结构和功能。尽管有53%的序列同源性，但小白蛋白与钙和镁的结合远不如大鼠小白蛋白紧密。更多位置特异的oncomodrin变体的产生和鉴定将进一步阐明在这个钙结合蛋白家族中负责离子结合亲和力的因素。这些结果不仅与钙结合蛋白有关，而且与蛋白质-配体的相互作用有关。先前研究的一个令人惊讶的结果是发现一种以前被称为禽类胸腺激素(ATH)的分子是小蛋白家族的成员，专门在胸腺中表达。禽类胸腺激素被认为能促进禽类T淋巴细胞成熟，但对其作用机制几乎一无所知。通过在骨髓前体细胞和/或未成熟淋巴细胞上识别ATH受体来追求这一发现是这项建议的第二个主要目标。受体的特性应该有助于深入了解小白蛋白样胸腺激素的生理意义。鸡的胸腺激素和肌肉相关的小白蛋白都是以组织特异性的方式表达的。比较两个小白蛋白基因中的调控序列和特定DNA结合蛋白的特征应该能为组织特异性基因表达的调控提供洞察力。小白蛋白是一种钙结合蛋白，被认为是肌肉中的细胞质钙离子缓冲器。有证据表明，它们在非肌肉组织中扮演着额外的、可能是调节的角色。这项研究旨在了解这些蛋白质的分子结构和细胞功能。这项研究的结果将为钙结合蛋白在细胞信号转导中作用的分子基础提供新的知识。

The parvalbumins were originally identified as calcium-binding cytoplasmic proteins in striated muscle where they are thought to function as calcium buffers. The subject of this research is the structure and function of two members of the parvalbumin family of proteins from non-muscle tissues. The parvalbumin, oncomodulin, binds calcium and magnesium far less tightly than rat parvalbumin, despite 53% sequence identity. Production and characterization of additional site-specific variants of oncomodulin will further elucidate the factors responsible for ion-binding affinity in this family of calcium binding proteins. These results should have relevance not only to calcium-binding proteins, but to protein- ligand interactions in general. A surprising result of prior studies was the finding that a molecule previously known as Avian Thymic Hormone (ATH) is a member of the parvalbumin family, expressed specifically in the thymus. Avian thymic hormone is believed to facilitate avian T-lymphocyte maturation, but virtually nothing is known about its mechanism of action. Pursuit of this finding by identifying a receptor for ATH on bone marrow precursor cells and/or immature lymphocytes is a second major goal of this proposal. Characterization of the receptor should provide insight into the physiological significance of the parvalbumin-like thymic hormones. Avian thymic hormone and the muscle-associated parvalbumin from chicken are both expressed in a tissue-specific manner. Comparison of regulatory sequences in the two parvalbumin genes and characterization of specific DNA-binding proteins should provide insight into regulation of tissue-specific gene expression. Parvalbumins are calcium-binding proteins believed to function as cytoplasmic calcium ion buffers in muscle. There is evidence to suggest that they play additional, possibly regulatory, roles in non-muscle tissues. This research is directed toward understanding the molecular structure and cellular function of these proteins. The results of this research will contribute new knowledge concerning the molecular basis for the role of calcium binding proteins in cellular signaling.