Structure−Function Relationship of the Fifth Transmembrane Domain in the Na+/H+Antiporter ofHelicobacter pylori: Topology and Function of the Residues, Including Two Consecutive Essential Aspartate Residues†

Biochemistry ◽  
2006 ◽  
Vol 45 (49) ◽  
pp. 14834-14842 ◽  
Author(s):  
Naoyuki Kuwabara ◽  
Hiroki Inoue ◽  
Yumi Tsuboi ◽  
Keiji Mitsui ◽  
Masafumi Matsushita ◽  
...  
Keyword(s):  
Structure Function ◽  
Transmembrane Domain ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
And Function ◽  
Relationship Of

A New Approach for Sequence Analysis

2011 ◽  
pp. 202-223 ◽  
Author(s):  
Kathryn Dempsey ◽  
Benjamin Currall ◽  
Richard Hallworth ◽  
Hesham Ali
Keyword(s):  
Sequence Analysis ◽  
Structure Function ◽  
Novel Structure ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
And Function ◽  
Traditional Approaches ◽  
Pathological Disease ◽  
Relationship Of

Understanding the structure-function relationship of proteins offers the key to biological processes, and can offer knowledge for better investigation of matters with widespread impact, such as pathological disease and drug intervention. This relationship is dictated at the simplest level by the primary protein sequence. Since useful structures and functions are conserved within biology, a sequence with known structure-function relationship can be compared to related sequences to aid in novel structure-function prediction. Sequence analysis provides a means for suggesting evolutionary relationships, and inferring structural or functional similarity. It is crucial to consider these parameters while comparing sequences as they influence both the algorithms used and the implications of the results. For example, proteins that are closely related on an evolutionary time scale may have very similar structure, but entirely different functions. In contrast, proteins which have undergone convergent evolution may have dissimilar primary structure, but perform similar functions. This chapter details how the aspects of evolution, structure, and function can be taken into account when performing sequence analysis, and proposes an expansion on traditional approaches resulting in direct improvement of said analysis. This model is applied to a case study in the prestin protein and shows that the proposed approach provides a better understanding of input and output and can improve the performance of sequence analysis by means of motif detection software.

A New Approach for Sequence Analysis

2013 ◽  
pp. 1536-1556
Author(s):  
Kathryn Dempsey ◽  
Benjamin Currall ◽  
Richard Hallworth ◽  
Hesham Ali
Keyword(s):  
Sequence Analysis ◽  
Structure Function ◽  
Novel Structure ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
And Function ◽  
Traditional Approaches ◽  
Pathological Disease ◽  
Relationship Of

Understanding the structure-function relationship of proteins offers the key to biological processes, and can offer knowledge for better investigation of matters with widespread impact, such as pathological disease and drug intervention. This relationship is dictated at the simplest level by the primary protein sequence. Since useful structures and functions are conserved within biology, a sequence with known structure-function relationship can be compared to related sequences to aid in novel structure-function prediction. Sequence analysis provides a means for suggesting evolutionary relationships, and inferring structural or functional similarity. It is crucial to consider these parameters while comparing sequences as they influence both the algorithms used and the implications of the results. For example, proteins that are closely related on an evolutionary time scale may have very similar structure, but entirely different functions. In contrast, proteins which have undergone convergent evolution may have dissimilar primary structure, but perform similar functions. This chapter details how the aspects of evolution, structure, and function can be taken into account when performing sequence analysis, and proposes an expansion on traditional approaches resulting in direct improvement of said analysis. This model is applied to a case study in the prestin protein and shows that the proposed approach provides a better understanding of input and output and can improve the performance of sequence analysis by means of motif detection software.

Role of aromatic residues in the structure-function relationship of .alpha.-bungarotoxin

Biochemistry ◽  
1982 ◽  
Vol 21 (11) ◽  
pp. 2592-2600 ◽  
Author(s):  
Yee Hsiung Chen ◽  
Jang Chyi Tai ◽  
Wan Jen Huang ◽  
Ming Zong Lai ◽  
Mien Chie Hung ◽  
...  
Keyword(s):  
Structure Function ◽  
Aromatic Residues ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Alpha Bungarotoxin ◽  
Relationship Of

Gene cloning and structure - function relationship of cytokines such as TNF and interleukins

1987 ◽  
Vol 16 (3-4) ◽  
pp. 219-226 ◽  
Author(s):  
Walter Fiers ◽  
Rudi Beyaert ◽  
Peter Brouckaert ◽  
Bart Everaerdt ◽  
Guy Haegeman ◽  
...  
Keyword(s):  
Structure Function ◽  
Gene Cloning ◽  
Structure Function Relationship ◽  
Function Relationship ◽  
Relationship Of

scholarly journals Pleiotropic functions of the transmembrane domain 6 of human melanocortin-4 receptor

2012 ◽  
Vol 49 (3) ◽  
pp. 237-248 ◽  
Author(s):  
Hui Huang ◽  
Ya-Xiong Tao
Keyword(s):  
Cell Surface ◽  
Structure Function ◽  
Transmembrane Domain ◽  
Mapk Pathway ◽  
Surface Expression ◽  
Camp Signaling ◽  
Cell Surface Expression ◽  
Melanocortin 4 Receptor ◽  
Function Relationship ◽  
Relationship Of

The melanocortin-4 receptor (MC4R) is a critical regulator of energy homeostasis and has emerged as a premier target for obesity treatment. Numerous mutations in transmembrane domain 6 (TM6) of MC4R resulting in functional alterations have been identified in obese patients. Several mutagenesis studies also provided some data suggesting the importance of this domain in receptor function. To gain a better understanding of the structure–function relationship of the receptor, we performed alanine-scanning mutagenesis in TM6 to determine the functions of side chains. Of the 31 residues, two were important for cell surface expression, five were indispensable for α-melanocyte-stimulating hormone (α-MSH) and β-MSH binding, and six were important for signaling in the Gs–cAMP–PKA pathway. H264A, targeted normally to the plasma membrane, was undetectable by competitive binding assay and severely defective in basal and stimulated cAMP production and ERK1/2 phosphorylation. Nine mutants had decreased basal cAMP signaling. Seven mutants were constitutively active in cAMP signaling and their basal activities could be inhibited by two MC4R inverse agonists, Ipsen 5i and ML00253764. Five mutants were also constitutively active in the MAPK pathway with enhanced basal ERK1/2 phosphorylation. In summary, our study provided comprehensive data on the structure–function relationship of the TM6 of MC4R. We identified residues that are important for cell surface expression, ligand binding, cAMP generation, and residues for maintaining the WT receptor in active conformation. We also reported constitutive activation of the MAPK pathway and biased signaling. These data will be useful for rationally designing MC4R agonists and antagonists for treatment of eating disorders.

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