Entropic Stabilization of Proteins and Its Proteomic Consequences

نویسندگان

  • Igor N. Berezovsky
  • William W. Chen
  • Paul J. Choi
  • Eugene I. Shakhnovich
چکیده

Evolutionary traces of thermophilic adaptation are manifest, on the whole-genome level, in compositional biases toward certain types of amino acids. However, it is sometimes difficult to discern their causes without a clear understanding of underlying physical mechanisms of thermal stabilization of proteins. For example, it is well-known that hyperthermophiles feature a greater proportion of charged residues, but, surprisingly, the excess of positively charged residues is almost entirely due to lysines but not arginines in the majority of hyperthermophilic genomes. All-atom simulations show that lysines have a much greater number of accessible rotamers than arginines of similar degree of burial in folded states of proteins. This finding suggests that lysines would preferentially entropically stabilize the native state. Indeed, we show in computational experiments that arginine-to-lysine amino acid substitutions result in noticeable stabilization of proteins. We then hypothesize that if evolution uses this physical mechanism as a complement to electrostatic stabilization in its strategies of thermophilic adaptation, then hyperthermostable organisms would have much greater content of lysines in their proteomes than comparably sized and similarly charged arginines. Consistent with that, high-throughput comparative analysis of complete proteomes shows extremely strong bias toward arginine-to-lysine replacement in hyperthermophilic organisms and overall much greater content of lysines than arginines in hyperthermophiles. This finding cannot be explained by genomic GC compositional biases or by the universal trend of amino acid gain and loss in protein evolution. We discovered here a novel entropic mechanism of protein thermostability due to residual dynamics of rotamer isomerization in native state and demonstrated its immediate proteomic implications. Our study provides an example of how analysis of a fundamental physical mechanism of thermostability helps to resolve a puzzle in comparative genomics as to why amino acid compositions of hyperthermophilic proteomes are significantly biased toward lysines but not similarly charged arginines.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Serratia marcescens B4A chitinase thermostability enhancement by S390I QuikChange site directed mutagenesis

Thermostable chitinases are useful for industrial and biotechnological applications. This paper reports the stabilization of chitinase from Serratia marcescens B4A through rational mutagenesis. Changing of Ser 390 to Ile in S. marcescens. The stabilization was enhanced through entropic stabilization by reduction of the loop length and also by increasing of the beta chain length. With this repla...

متن کامل

Proteomic Analysis of Gene Expression in Basal Cell Carcinoma

Background: Basal Cell Carcinoma (BCC) is a type of non-melanoma skin cancer. Alteration in gene expression is the important event that happens in cancer cell. Detection of this event is possible by proteomics techniques. Methods: Normal and tumor tissues were taken from BCC patient. Total proteins were purified by standard methods, and proteins were separated by two-dimensional electrophoresis...

متن کامل

Comparative Proteomic Analysis of Two Manilkara Species Leaves Under NaCl Stress

Background: Salinity is a major environmental limiting factor, which affect agricultural production. The two Manilkara seedlings (M. roxburghiana and M. zapota) with high economic importance, could not adapt well to higher soil salinity and little is known about their proteomic mechanisms. Objectives: The mechanisms responsible ...

متن کامل

Alpha-1 antitrypsin, retinol binding protein and keratin 10 alterations in patients with psoriasis vulgaris, a proteomic approach

Objective(s):Psoriasis is an autoimmune disease that appears on the skin. Although psoriasis is clinically and histologically well characterized, its pathogenesis is unknown in detail. The aims of this study were to evaluate the proteome of psoriatic patients' sera and to compare them with those of normal healthy human to find valuable biomarkers. Materials and Methods: In a case-control study,...

متن کامل

Serum Proteomic Profiling of Obsessive-Compulsive Disorder, Washing Subtype: A Preliminary Study

Introduction: Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD. Methods: Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • PLoS Computational Biology

دوره 1  شماره 

صفحات  -

تاریخ انتشار 2005